Structure and biological activity of prebiotics.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Toxicity, Human Health and Environment",slug:"nanomaterials-toxicity-human-health-and-environment",publishedDate:"February 19th 2020",bookSignature:"Simona Clichici, Adriana Filip and Gustavo M. do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/8137.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"64160",title:"Prof.",name:"Simona",middleName:null,surname:"Clichici",slug:"simona-clichici",fullName:"Simona Clichici"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"251730",title:"Dr.",name:"Guilherme",middleName:"Fredeico Bernardo",surname:"Lenz E Silva",fullName:"Guilherme Lenz E Silva",slug:"guilherme-lenz-e-silva",email:"guilhermelenz@usp.br",position:null,institution:null},{id:"286148",title:"Dr.",name:"Camila",middleName:null,surname:"Viana",fullName:"Camila Viana",slug:"camila-viana",email:"camilaoviana@gmail.com",position:null,institution:{name:"Centro de Desenvolvimento da Tecnologia Nuclear",institutionURL:null,country:{name:"Brazil"}}},{id:"286149",title:"Dr.",name:"Fernanda",middleName:null,surname:"Vieira",fullName:"Fernanda Vieira",slug:"fernanda-vieira",email:"fevieira2001@gmail.com",position:null,institution:{name:"Centro de Desenvolvimento da Tecnologia Nuclear",institutionURL:null,country:{name:"Brazil"}}},{id:"286151",title:"M.Sc.",name:"Danieli",middleName:"Silva",surname:"Domingues",fullName:"Danieli Domingues",slug:"danieli-domingues",email:"danielisilva@ymail.com",position:null,institution:{name:"Centro de Desenvolvimento da Tecnologia Nuclear",institutionURL:null,country:{name:"Brazil"}}}]},book:{id:"8137",title:"Nanomaterials",subtitle:"Toxicity, Human Health and Environment",fullTitle:"Nanomaterials - Toxicity, Human Health and Environment",slug:"nanomaterials-toxicity-human-health-and-environment",publishedDate:"February 19th 2020",bookSignature:"Simona Clichici, Adriana Filip and Gustavo M. do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/8137.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"64160",title:"Prof.",name:"Simona",middleName:null,surname:"Clichici",slug:"simona-clichici",fullName:"Simona Clichici"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11844",leadTitle:null,title:"Quartz - From Mineral Deposits to Industry",subtitle:null,reviewType:"peer-reviewed",abstract:"\r\n\tCurrently, both in science and in industry, quartz has numerous applications that continue to grow in line with technological development. In the same way, the specifications that are considered in the mineral raw material markets are diversified, from very restrictive quality, for high-tech artifacts, to the most eclectic for abrasives and glass-ceramic applications. In the same way, the diversity of contaminations that are accepted in the different industrial batches are very varied and imply a great diversity of application and behavior tests in transformation routines.
\r\n\r\n\tFrom the outset, natural sources are more suitable for some applications, but in any case, it is necessary to ensure deposits with large monomineralic masses, as homogeneous and pure as possible, which allow viable mining in both quantity and quality. These conditions tend to occur mainly in granitic pegmatitic deposits and in metamorphic or hydrothermal quartz veins. Furthermore, more and more ornamental varieties of quartz enter architecture, design, and jewelry.
\r\n\r\n\tIt is proposed here to present a holistic view of quartz from its descriptive mineralogy to industrial applications, including the origin and characteristics of the different types of mineral deposits and the physicochemical performance tests that distinguish the quartz batches for different forms of application with consequences for the marketing of the corresponding raw materials.
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In the last 26 years, he has done at least one annual mission for the study of geology, prospecting, and mining in Portuguese-speaking countries (Brazil, Mozambique, and Angola) supporting several mining companies based there.",institutionString:"University of Minho",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Minho",institutionURL:null,country:{name:"Portugal"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"247865",firstName:"Jasna",lastName:"Bozic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/247865/images/7225_n.jpg",email:"jasna.b@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Besides the push towards replacement of chemical additives by those obtained from natural sources, this awareness has led to a rising demand for enrichment of foods with bioactive compounds that have beneficial effects on human health [1]. Therefore, nowadays, a variety of gluten free and products enriched with dietary fiber, or containing probiotics and/or prebiotic and functional oligosaccharides are available in the market [2].
Oligosaccharides are carbohydrates, composed of up to twenty monosaccharides linked by glycosydic bonds, widely used in food and pharmaceutical industries. These compounds are obtained from natural sources and through chemical or biotechnological processes [3,4].
Among the various functions of non-digestible oligosaccharides, one that has attracted attention is its prebiotic potential. A prebiotic can be defined as “selectively fermented ingredients that allow specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host well-being and health” [5]. An oligosaccharide to be regarded as prebiotic must not be hydrolyzed or absorbed in the upper part of the gastrointestinal tract; and must be assimilated selectively by one or by a limited number of beneficial microorganisms in the colon, promoting benefic luminal or systemic effects. To improve colonic function, live microorganisms can be administered in adequate amounts, being known as probiotics; and to be used in food, these organisms must be able to survive passage through the gut; to proliferate and to colonize the digestive tract; and must be safe and effective [6,7].
The intestinal benefits of prebiotics, such as fructooligosaccharides and inulin as well as their symbiotic association with probiotic bacteria, encompass prevention and treatment of infectious diseases, including viral or bacterial diarrhea, and chronic inflammatory diseases such as ulcerative colitis [8]. The mechanisms of action of probiotics against gastrointestinal pathogens consist mainly on competition for nutrients and sites of access, production of antimicrobial metabolites, changes in environmental conditions, and modulation of the immune response of the host. Other benefits attributed to prebiotics and probiotics include treatment of inflammatory intestinal and irritable bowel syndrome, prevention of cancer, and modulation of the immune system, mineral absorption and lipid metabolism [8,9].
Oligosaccharides can be obtained by extraction from natural sources (milk, vegetables, fruits), and by chemical or biotechnological processes [10,11]. Mixtures of oligosaccharides with different degrees of polymerization and glycosidic linkages are usually formed in the enzymatic processes. Chemical structures and composition of these mixtures depend on the type and source of enzymes, and on process conditions, including the initial concentration of substrate [11,12]. Depending on the initial substrate, production of oligosaccharides can involve different steps: hydrolysis of glycosidic bonds giving rise to monomers, followed by generation of disaccharides and other oligomers through the action of transferases [13,14].
Fructans are carbohydrates in which one or more fructosylfructose links constitute the majority of glycosidic bonds [15]. These carbohydrates can be of the inulin-type with β-(2,1)-D-fructofuranosyl units, found in plants and synthesized by fungi. Additionally, there are the levan-type fructans with β-(6,2)-D-fructofuranosyl units, found in plants and synthesized by bacteria [16].
Levan is a polymer with very high molecular weight that can reach 107 Da [17]. In contrast to levan, inulin from chicory consists of a mixture of oligomers and polymers with a degree of polymerization (DP) that varies from two to approximately sixty units (Figure 1; Table 1) [18]. Around 10% of the fructan chains in native chicory inulin have a DP in the range between two and five [5].
Structure of inulin, a linear fructosyl polymer linked by β-(2,1) bonds (n=3-65), attached to a terminal glucosyl residue by an α-(1,2) bond.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
FOS | \n\t\t\tFructosyl units linked by β-(2,1) bonds, attached to a terminal glucosyl residue by α-(1,2) bond (Variants: Inulin type β-1,2 and Levan type β-2,6 linkages between fructosyl units in the main chain) DP=3-10. | \n\t\t\tSoluble fibers; Gel formation; Sugar replacement; Moderate sweetness; Stable (depending on matrix). | \n\t\t\tPrevention of intestinal infections and extra intestinal infections (e.g. respiratory tract; Inhibition of pathogens, ordering intestinal flora; Regulation of intestinal immune system; Enhancement of immune response; Stimulation of probiotic growth of Lactobacilli and Bifidobacteria species; Optimization of colonic function and metabolism; Production of short chain fatty acids; Increase of mineral absorption; Reduction of food intake and obesity management and control of diabetes type 2; Prevention of cancer. | \n\t\t\t[8,24,25, 61,67,69, 72,170, 176-186] | \n\t\t
Inulin | \n\t\t\tMixture of linear fructosyl polymers and oligomers (DP = 3-65) linked by β-(2,1) bonds, attached to a terminal glucosyl residue by α(1—2) bond. | \n\t\t\tSoluble fiber; Water adsorption; Gel formation; Modifier of viscosity, texture, colour and sensory aspects of food formulations; Replacement for fat and sugar; Low calorimetric value; Moderate sweetness. | \n\t\t\tStimulation of probiotic growth; Lowering effect on cholesterol LDL and triglycerides levels; Influence on inflammatory markers and development of gut associated lymphoid tissue (GALT); Regulation of intestinal immune system; Enhancement of immune response; Increase of mineral absorption (Calcium, Iron and Magnesium); Prevention of cancer. | \n\t\t\t[8,19,67, 176,187-195] | \n\t\t
GOS | \n\t\t\tMixture of galactopyranosyl oligomers (DP= 3-8) linked mostly by β-(1,4) or β-(1,6) bonds, although low proportions of β (1,2) or β-(1,3) linkages may also be present. Terminal glucosyl residues are linked by β-(1,4) bonds to galactosyl units. | \n\t\t\tStable in acidic conditions and in higher temperatures; Soluble; Cryoprotector activity; Low ability to crystalyze; Incorporated in various functional foods. | \n\t\t\tStimuli of probiotic growth; Reorder intestinal flora; Regulation of intestinal immune system; Reinforcement of intestinal barrier; Inhibition of adhesion of pathogens; Mimic molecular receptors, inhibit microbial adherence; Prevent infections (e.g. Prevention of cancer; Enhance mineral absorption; Reduce food intake, helping obesity management. Use in diabetic foods, free from carbohydrates that increase the level of postprandial glucose; Use in specialized foods for individuals intolerant to lactose. | \n\t\t\t[8,105, 196- 206] | \n\t\t
Lactulose | \n\t\t\tGalactosyl β-(1,4) fructose. | \n\t\t\tSweetener, sugar replacement; | \n\t\t\tInduces growth of use as laxative in the treatment of constipation; Optimization of colonic function and metabolism, reducing colon pH and ammonia concentration; Increased mineral absorption; Treatment of portal systemic encephalophathy and chronic constipation; Uses in diabetic and dairy foods. | \n\t\t\t[205, 207-211] | \n\t\t
COS | \n\t\t\tChitin: β-(1,4) linked N-acetyl-D-glucosamine residues; Chitosan: β-(1,4) linked D-glucosamine polymer. DP=2-8 | \n\t\t\tAntimicrobial activity of chitosan depends on degree of polymerization, amino groups content and degree of acetylation; Chelation of metal trace elements and essential nutrients; Flocculation and adsorption capacity mainly because of the cationic macromolecular structure. | \n\t\t\tAntimicrobial and antioxidant activity; Use as food preservative; Use as dietary supplements in functional foods; Prebiotic activity; Hypocholesterolemic; | \n\t\t\t[149, 212, 213] | \n\t\t
XOS | \n\t\t\tXylose oligomers connected by β-(1,4) linkages (DP=3-6). | \n\t\t\tStable in a large range of pH values (2,5-8,0); Thermal stability (up to 100°C); Antioxidant effects; Antifreezing activity; Low cariogenicity; Low calorimetric value; Low glycemic index. | \n\t\t\tInhibition of pathogens growth, reordering intestinal flora; Stimulation of probiotic growth; Reinforcement of intestinal barrier; Optimization of colonic function and metabolism; Obesity management, reduction of food intake and weight. | \n\t\t\t[159, 162, 179, 214-216] | \n\t\t
IMO | \n\t\t\tGlucosyl residues linked to maltose or isomaltose by α-(1,6) glycosidic bonds. | \n\t\t\tLow sweetness; Low viscosity; Bulking properties; Humectant; Prevention of sucrose crystallization. | \n\t\t\tOptimization of colonic function and metabolism, reduces nitrogenated products; Increase caecum weight; Antidiabetic effects; Improve lipid metabolism and obesity management. | \n\t\t\t[2, 217- 219] | \n\t\t
SOS | \n\t\t\tOligomers composed by galactosyl units linked to sucrose by α-(1,6) bonds. Most abundant are raffinose and stachyose. | \n\t\t\tStabilizer properties; Cryoprotectant effect. | \n\t\t\tPrevention of pathogen proliferation. | \n\t\t\t[2, 156, 213, 220, 221] | \n\t\t
Structure and biological activity of prebiotics.
FOS: Fructooligosaccharides; GOS: Galactooligosaccharides; COS: Chitooligosaccharides;
XOS: Xylooligosaccharides; IMO: Isomaltooligosaccharides; SOS: Soybean oligosaccharides
Inulin-type fructooligosaccharides are made up of two or more fructosyl moieties linked by β-(2,1) bonds and united at the non-reducing end to a terminal glucose residue by an α-(1,2) glycosidic bond (Table 1) [19]. The term fructooligosaccharides (FOS) is mainly used for fructose oligomers that contain one glucose unit and from two to four fructose units bound together by β-(2,1) glycosidic linkages [20,21]. Nevertheless, oligofructose and FOS may be regarded as synonyms for the mixture of small inulin oligomers with DP<10 [6,22]; while short chain FOS (sc-FOS) are fructose oligomers mainly composed of 1-kestose (GF2), nystose (GF3), and 1F-fructofuranosylnystose (GF4) (Figure 2) [23-25].
Structures of typical fructooligosaccharides (FOS), derived from sucrose. FOS consist of a glucosyl residue α-(1,2) linked to two or more β-(1,2) fructosyl units. Synthesis of these FOS is catalyzed by fructosyltransferases, requiring a second sucrose molecule as a fructosyl residue donor.
Fructans have storage and protective functions in many commonly consumed plants, being a typical part of the diet. Some food sources are richer in high molecular weight fructans, such as inulin, while others have higher levels of sc-FOS [26].
FOS are found in low levels in natural sources such as asparagus, sugar beet, garlic, chicory, onion, Jerusalem artichoke, wheat, honey, banana, barley, tomato, and rye [27-29]. Apart from usually occurring in low concentrations, seasonal conditions also limit their large-scale production from these sources [30].
For this reason, enzymatic processes are used for the industrial production of FOS. One route involves the controlled hydrolysis of long chain fructans (Table 2) [31,32], which results in a large amount of FOS mostly without glucose in their structures. The other route is the synthesis from sucrose, which leads to sc-FOS that contain a molecule of glucose in their structures [11,33]. The present review will focus on the synthesis of FOS from sucrose.
FOS are produced from sucrose by the action of microbial enzymes with high transfuctosylating activity: β-D-fructosyltransferase (FTase, EC 2.4.1.9) and β-fructofuranosidase (FFase, EC 3.2.1.26) (Table 2) [34]. Since FTase possesses almost only the transfructosylating activity, it is able to cleave the β-1,2 linkage of sucrose, transferring the fructosyl group to an acceptor molecule, with the resulting formation of fructooligosaccharides and release of glucose [35]. This enzyme shows little affinity towards water as an acceptor, therefore the hydrolase activity of FTase is very low [36].
FFase can catalyze both hydrolytic and transfructosylating reactions, nevertheless, transfructosylation only takes place when sucrose concentrations are higher than 500 g L-1 [27,34,36-38]. The production of FOS by the action of FFase on sucrose can occur either by reverse hydrolysis or by transfructosylation [36].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
FOS | \n\t\t\tEnzymatic reactions: fructosyltransferases using sucrose as a substrate or from inulin using microbial endoinulinases. | \n\t\t\tFructosyltransferases or β-fructofuranosidases; Levansucrases; Endoinulinases. | \n\t\t\t\n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t | \n\t\t\tNeosugar Actilight NutraFlora P-95 - GTC Nutrition Raftilose P95 - Orafti Group | \n\t\t\t[21,29, 170, 176, 222] | \n\t\t
Inulin | \n\t\t\tNatural product, extraction from plants | \n\t\t\tNot applicable | \n\t\t\tNot apllicable | \n\t\t\tInulin-S – SigmaAldrich Fibruline - Trades S.A. Fibrex - Danisco Sugar Frutafit CLR DP8, Fruta- fit HD DP10, Frutafit TEX DP5, Inulin TEX – Sensus Inulin GR, HP, HP-gel, HPX, LS, ST, Raftilin ST, Raftilose P95, Raftiline HP - Orafti Group | \n\t\t\t[189, 194, 222] | \n\t\t
GOS | \n\t\t\tEnzymatic transgalactosylation reactions, using lactose as substrate; Fermentation process. | \n\t\t\tβ-Galactosidases | \n\t\t\t\n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t | \n\t\t\tVivinal GOS Syrup - Bolculo Domo or Friesland Foods Domo Purimune - GTC Nutrition Oligomate 55NP - Yakult Pharmaceutical Inc. Cup Oligo H-70® Kowa Company BiMuno - Clasado Ltd. | \n\t\t\t[105,120, 198, 202-205, 223- 227] | \n\t\t
Lactulose | \n\t\t\tThermal-alkaline isomerisation of lactose; Enzymatic transgalactosylation of fructose. | \n\t\t\tβ-Galactosidases β-Glycosidases | \n\t\t\t\n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t | \n\t\t\tSigma Aldrich Discovery Fine Chemicals Solvay | \n\t\t\t[209, 210, 228-230] | \n\t\t
XOS | \n\t\t\tEnzymatic degradation of xylans | \n\t\t\tEndo-β-1,4-xylanases, exo-β-1,4-xylosidases, α-glucuronosidases, α-L-arabinofuranosidases, acetylxylan esterases, ferulic acid esterases and p-coumaric acid esterases. | \n\t\t\t\n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t | \n\t\t\tXylooligo™- Suntory Ltd. YOGHURINA -Suntory Ltd. MARUSHIGE GENKISU - Marushige Ueda Co. L-ONE - Enzamin Laboratory Inc. SUKKIRI KAICHO Lotte Co. | \n\t\t\t[152, 159, 232] | \n\t\t
COS | \n\t\t\tEnzymatic or chemical depolimerization and deacetylation of chitin and chitosan | \n\t\t\tChitosanases and other non-specific enzymes (papain, and lysozyme) | \n\t\t\t\n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t | \n\t\t\tQingdao BZ-Oligo Co, Ltd. BioCHOS. AMSBIO | \n\t\t\t[213 232-235] | \n\t\t
SOS | \n\t\t\tDirectly extracted from soybean | \n\t\t\tNot applicable | \n\t\t\tNot applicable | \n\t\t\tSoya-oligo - The Calpis Food Industry Co. | \n\t\t\t[152] | \n\t\t
IMO | \n\t\t\tEnzymatic hydrolysis of starch | \n\t\t\tα-Amylases or pullulanases, β-amylases and α-glucosidases in sequence. Pullulanases | \n\t\t\t\n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t \n\t\t\t\t | \n\t\t\tIsomalto-900 - Showa Sangyo | \n\t\t\t[12, 152, 159, 236] | \n\t\t
Obtention and industrial production of prebiotics.
FOS are produced at industrial scale from concentrated sucrose solutions using fungal transfructosylating enzymes mainly from strains of
The enzymes from
Catalytic and physicochemical properties of the producing enzymes, as well as production conditions and composition of FOS are different, depending on the microbial strain. For instance, fungal FTases have molecular masses ranging between 180,000 and 600,000, and are homopolymers with two to six monomer units [43].
Fructosyltransferase from
A transferase isolated and purified from
The theoretical yield of FOS from sucrose is 75% if 1-kestose is the only FOS produced [46]. However, production yields of FOS are typically low (55–60%) due to the hydrolytic activity which gives rise to glucose and fructose as reaction byproducts [27] and/or to the fact that glucose acts as an inhibitor of the enzymes, reducing the reaction efficiency [36,47,48]. To improve FOS production yields, glucose oxidase has been used to remove glucose via transformation to gluconic acid [49] and glucose isomerase has been used to interconvert glucose to fructose [46]. Nevertheless, it is necessary to seek for strains among the microbial diversity with high transfructosylating activity, able to produce high yields of oligosaccharides and low yields of monomeric sugars [35].
In addition, the supply of sc-FOS is limited compared to their increasing demand in the food industry, because enzymes such as fructosyltransferases are not widely commercially available [50]. For this reason, the production of FOS is usually carried out in a two-stage process, in which the first stage consists of the microbial production of the enzyme with transfructosylation activity, while the second involves the reaction of the produced enzyme with sucrose (substrate) to generate FOS [29].
A commercial pectinase preparation from
Enzymes from
In a recent study, twenty-five commercial enzyme preparations used in the food industry were screened for transfructosylation activity. Three preparations showed high transfructosylation activity from sucrose, high ratios of transferase over hydrolase activity, selectivity for the synthesis of sc-FOS and did not hydrolyze the produced sc-FOS after a 12 h reaction time [55]. Among these enzymes, a cellulolytic enzyme preparation, Rohapect CM, catalyzed the synthesis of sc-FOS with relatively high production yield (63.8%), under cost-effective conditions of temperature (50°C), sucrose concentration (2.103 M) and enzyme concentration (6.6 TU/mL), which could provide a process with potential application at industrial scale [50].
The synthesis of FOS from sucrose is economically advantageous because sucrose is less expensive than inulin; however, the use of enzymes as catalysts for industrial processes is expensive. Furthermore, the recovery of soluble enzymes for reuse is not economically feasible. In contrast, enzyme immobilization usually confers high storage and long-term operational stability, facilitates the recovery and reuse of the biocatalyst, allowing a cost-efficient use of the enzyme in continuous operation, among other advantages [56,57].
In this context, the commercial enzyme preparation from
Synthesis of FOS by dried alginate entrapped enzymes (DALGEEs) was recently reported [60]. FTase from
A partially purified β-fructofuranosidase from the commercial enzyme preparation Viscozyme L was covalently immobilized on glutaraldehyde-activated chitosan particles [61]. Thermal stability of the immobilized biocatalyst was around 100-fold higher at 60°C when compared to the free enzyme. The biocatalyst also showed a high operational stability, which allowed its reuse for at least 50 cycles without significant loss of activity. The average yield of FOS production from sucrose was 55%.
An alternative to the enzymatic production of FOS is the use of either free or immobilized whole cells in bioreactors [62]. Production of these oligosaccharides via fermentation processes has the advantage of obviating purification of FOS-producing enzymes from the cell extracts [29,63,64].
An integrated one-stage method for production of FOS via sucrose fermentation by
Two filamentous fungi,
Two food companies in Japan and Korea use different commercial processes for the continuous production of FOS with immobilized cells of
Immobilization of whole cells of
Several important health benefits are associated with the consumption of FOS as food ingredients. These include modulation of colonic microflora; improvement of the gastrointestinal physiology; activation of the immune system; enhancement of the bioavailability of minerals; reduction of the levels of serum cholesterol, triglycerides and phospholipids; and prevention of colonic carcinogenesis [34,44,67,68].
Among the different FOS, 1-kestose is considered to have better therapeutic properties than those with higher degree of polymerization [69]. The chain length is an important factor influencing the physiological effect of the oligomer in the host [69] and fermentation by bifidobacteria and lactobacilli species [70].
In this context, fermentation of oligosaccharides was evaluated using pure FOS mixtures containing three FOS species (GF2, GF3 and GF4). Only two oligosaccharides (GF2 and GF3) were consumed by
Moreover, β-fructofuranosidase activity enables bifidobacteria to degrade FOS. Nevertheless, this property is strain-dependent. Some strains consume both fructose and oligofructose, with different preferences and degradation rates [72].
FOS can be used as calorie-free and non-carcinogenic sweeteners. 1-Kestose has enhanced sweetening power compared to other sc-FOS, and 1-kestose-rich sc-FOS syrups can be used as sugar for diabetics [27,73].
Other types of FOS, such as the levan-type and the neo-FOS, have very promising properties; however, they are not yet commercially available [53,74,75].
Lactose is a disaccharide formed by the condensation of glucose and galactose molecules, and is the most important component of mammalian milk, present in a concentration range from 2.0% to 10%. Lactose can be obtained at industrial scale from whey during cheese production, with dry weight around 80-85%, using crystallization techniques [76-78]. In the past, whey was considered a waste, although, nowadays, it is used to produce whey powders products, improving economic and environmental aspects of the by-products [79].
Lactose presents a great importance for food and pharmaceutical industries, being used in various food products such as chocolate, confectionary and other processed products, as well as carrier of medicines in dry powder inhalation preparations, excipient of tablets [80]. In humans, lactose can cause abdominal discomfort due to its maldigestion, which reaches approximately 70% of the world’s adult population [81]. β-Galactosidase (β-D-galactoside galactohydrolase, E.C. 3.2.1.23) plays an important role in human health because it is able to catalyze the hydrolysis of lactose in glucose and galactose, and because of that, it is often referred to as lactase. In addition, the transglycosylation reaction can also occur, in which galactooligosaccharides (GOS) are produced, and their structures can differ in regiochemistry of glycosidic linkage and degree of polymerization (Figures 3-5; Tables 1 and 2) [82,83].
Structure of a galactooligosaccharide (GOS) derived from lactose, a β-(1,4) linked galactosyl oligomer (n=1-4), attached to a terminal glucosyl residue by a β-(1,4) bond. GOS are synthesized by the reverse action of β-galactosidases on lactose in higher concentrations.
Examples of structures of galactooligosaccharides: 4-galactosyl lactose (top) and 6-galactosyl lactose (bottom) are represented, showing usual regiochemistry differences in galactosyl linkages.
Enzymatic synthesis of GOS by transgalactosylation reactions. Transgalactosylation is the transfer of the galactosyl residue, after the cleavage of lactose, to an acceptor molecule containing a hydroxyl group. When the acceptor is water (A), a galactose is formed by lactose hydrolysis, whereas if the acceptor is a sugar, a disaccharide or a GOS may be formed. In intramolecular transgalactosylation (B), galactosyl donor and acceptor are the same (glucose), only linkage position changes. In intermolecular transgalactosylation (C), there is an enzymatic transfer to another nucleophilic acceptor (Y), which can be all the sugars present in the reaction media, resulting in GOS mixtures.
Despite the fact that enzymes such as β-glycosidases and β-glucosidases, which also hydrolyze carbohydrates, are able to catalyze transglycosylation reactions, β-galactosidase is the most used enzyme in dairy industry to produce GOS. β-galactosidases from
Galactooligosaccharides can be defined as a mixture of substances produced from lactose, with two to eight saccharide units, in which one of the units is a terminal glucose and the remaining units are galactose and disaccharides comprising two units of galactose [85]. Several of these GOS are recognized as prebiotics, because they are non-digestible saccharides and can be used selectively by bifidobacteria and lactobacilli in human intestine, and thus improve host health [86, 87].
Conversion of lactose into GOS is catalyzed by β-galactosidases in a kinetically controlled reaction that involves competition between hydrolysis and transgalactosylation. The thermodynamically favored hydrolysis of lactose, which generates D-galactose and D-glucose, competes with the transferase activity that produces a complex mixture of galactose-based di- and oligosaccharides. Transgalactosylation involves direct galactosyl transfer (intramolecular reaction) to D-glucose yielding regio-isomers of lactose, and indirect transgalactosylation (intermolecular) giving rise to disaccharides, trisaccharides, and tetrasaccharides, and eventually longer GOS. The interaction in the active site of the enzyme differs with the acceptor. When the acceptor is water, glucose and galactose are formed; whereas if the acceptor is a sugar, reaction results in GOS [86, 87].
Therefore, high lactose concentrations and low water contents are favorable for GOS synthesis, being the initial lactose concentrations the most important factor, independently of the enzyme source. In general, higher lactose concentrations than 30% are necessary to favor synthesis over hydrolysis [87]. However, at the same lactose concentrations, different yields of GOS can be obtained, because β-galactosidases from different sources, with different structures and/or mechanisms, exhibit different selectivity for water and saccharides. Moreover, GOS yields depend on process conditions, such as temperature, reaction time, pH and enzyme/substrate ratio [88]. However, GOS production can be affected by glucose and/or galactose that are recognized as inhibitors of hydrolysis for many β-galactosidases [89,90].
The reaction time and initial concentration of lactose are considerably important to favor GOS production, since they are simultaneously synthesized and hydrolyzed by β-galactosidase, being regulated by the kinetics of synthesis and hydrolysis. Additionally, lactose concentration can increase formation of GOS due to increased availability of galactosyl and decreased availability of water [82,91]. Additionally, reverse micelle systems, in which the enzyme is entrapped in an aqueous micelle surrounded by organic solvent, provide decrease of the thermodynamic activity of water [92,93]. Chen et al. 2003 [93] reported that the transgalactosylation capability of low concentrations of β-galactosidase and lactose, operating in reverse micelles system, was similar to high concentrations of enzyme and substrate in an aqueous system. Authors also showed that GOS production decreases with the increase in water content.
Production of GOS can be improved increasing the reaction temperature. Lactose has relatively low solubility at room temperature, which increases with increasing temperature. Therefore high temperatures are desirable since they allow the increase of lactose concentration [94,95]. Besides the possibility to increase the solubility of subtracts and products, high temperature is advantageous due to the reduced risk of microbial contamination, lower viscosity and improved transfer rates [96]. However, this is not a general rule, Boon et al. (1998) [97] reported that the increase of initial lactose concentration achieved at high temperature does not influence GOS yield using β-galactosidase from
Another strategy to decrease water activity, and carry out catalysis with both high lactose concentration and temperature, demonstrated by Maugard
Similarly to temperature, pH value can affect the GOS yield, possibly through the control of synthesis and degradation [105] According to Huber
In general, oligosaccharides, including galactooligosaccharides, are produced using sucrose or starch, whey, among other substrates with high quality and low cost. The process designed to convert raw material into oligosaccharides must be inexpensive and focused on increasing the productivity and stability of enzymes. In this context, immobilization of biocatalysts can reduce the process costs due to some advantages; such as possibility to reuse the biocatalyst, applying a series of batchwise or continuous reactions; the biocatalyst can exhibit more stability than the native counterpart; besides this, immobilization can reduce costs of downstream, since separation of the biocatalyst from the product can be minimized [108-110]. Recently, several authors have employed immobilized β-galactosidase to produce GOS, applying different strategies with promising results [111-114]. Urrutia et al (2013) [111] immobilized
Smart polymers have been studied to develop GOS production processes. Poly-N-isopropyl acrylamide is a thermo-responsive poly-N-isopropyl acrylamide (PNIPAAm), which presents good solubility in water and distinct phase transition at its lower critical solution temperature (LCST). It is applied in different areas, such as medicine, biotechnology, and engineering [115,116]. Based on these advantages, Palai et al (2014) [117] developed a useful bioconjugate between PNIPAAm and β-galactosidase. The constructed PNIPAAm-β-galactosidase (PNbG) can be used in catalysis and, after that; it can be easily separated from the solution by heating at a temperature above its LCST. Further on, Palai et al (2015) [118] continued the GOS production research using this bioconjugate. A maximum GOS yield of 35 % was obtained at pH 6 and 40°C. An increase in GOS yield was observed when the temperature was risen from 30 to 40°C. At 45°C or above, after prolonged time, enzyme deactivation occurred. Moreover, bioconjugates could be reutilized at least ten times; and the separation was done by simple decantation after addition of 0.05 M NaCl and heating at 40°C.
The use of resting or living cells for GOS production appears to be interesting due to its low cost when compared to the use of purified enzyme. Despite the complexity of biocatalysis processes involving whole cells, glucose and galactose can be consumed by them. The consumption of the monosaccharides is interesting because their presence in foods is undesirable, since they do not exhibit prebiotic effect, increase caloric value of food, and can inhibit the activity of certain β-galactosidases [119].
Nevertheless, the use of whole cells can be exploited in order to selectively improve GOS production [120]. Beta-galactosidase form
Products containing GOS were launched for the first time in Japan in the 1980s. Due to their various and important health benefits, applications of GOS gradually increased worldwide. These oligosaccharides can be found in diverse products such as yogurt, bakery products, beverages, snack bars among others [122]. GOS are able to stimulate the growth of bifidobacteria and lactobacilli in the lumen despite other members of the microbiota that were considered potentially harmful. These oligosaccharides can prevent bacterial adherence due to their properties of mimicking host cell receptors in which bacterial adhesion occurs [123]. GOS can hinder the development of colon cancer, effect which can be attributed to their capacity of delaying fermentation processes, and reducing the activity of genotoxic bacterial enzymes associated with this disease [124]. Mineral absorption can be stimulated by GOS administration, and their effect on calcium absorption was verified. GOS can be used to alleviate constipation, which is relatively common in elderly people and pregnant women. It occurs due to increased bacterial growth and fecal weight; besides this, short fatty acids stimulate intestinal peristalsis and increase osmotic pressure of fecal weight. Moreover, GOS have been reported as indirectly acting on mucosal and systemic immune activity, and also as having protective effects against allergic manifestations [125].
In the last years, studies of production and application of chitooligosaccharides (COS) have increased due to their biodegradability, biorenewability, biocompatibility, physiological inertness and hydrophilicity, properties that serve as a basis for the use of COS as functional food or to preserve food from degradation.
Chitin is one of the most abundant natural compounds on earth and its production is mainly based on the extraction from marine species (shrimps, crabs, lobsters, krills, etc.) [126]. Chitin is a copolymer of N-acetyl-D-glucosamine and D-glucosamine units linked by β-(1,4) glycosidic bonds, where N-acetyl-D-glucosamine units are predominant in the polymeric chain as shown in Figure 6A [127]. Chitin obtained from natural sources has a complex composition, containing several minerals, proteins, lipids, pigments and other compounds. Chitosan, an important derivative from chitin, is the deacetylated form of chitin, where N-acetyl groups are removed by chemical methods (Figure 6B).
Structures of chitooligosaccharides (n= 3-7), A – Chitin (β-1,4-linked N-acetyl-D-glucosamine residues); B – Chitosan (β-1,4-linked D-glucosamine polymer).
A considerable amount of residues from processing of fish and crustaceans, rich in chitin and chitosan, are considered hazardous wastes and at the same time have high potential commercial value as raw material [128]. It is possible to obtain chitooligosaccharides from those residues, after prior demineralization and deproteinization by acid and alkali treatments [129].
Chitooligosaccharides are produced by chemical methods or by enzymatic methods from chitosan, produced by alkaline N-deacetylation. At industrial scale, the chemical route is used to produce chitooligosaccharides; however, this methodology presents several disadvantages such as high cost, low yield due to indiscriminate breaks of the polymer chain, production of toxic compounds due to modification on the chitin structure, as well as, corrosion and environmental hazards [130].
The enzymatic process is an attractive solution to overcome the above-mentioned disadvantages, due to their specific action on the substrate, despite the economic costs. Enzymatic hydrolysis of chitin or chitosan involves several enzymes: chitinase, chitosanase, lysozyme and cellulase [131]
According to Mourya
Global flow chart for production of COS by enzymatic hydrolysis of chitin and chitosan (adapted from Jung and Park 2014 [
Chitnases are chitinolytic enzymes hydrolyzing the glycoside bonds between the sugars, which have the unique capacity to hydrolyze the GlcNAc-GlcNAc (2-acetamido-2-deoxy-β-D-glucose) links. Pre-treatment with acid solution is necessary to break down the crystalline structure of chitin and increase the availability of substrate to the action of enzymes. Chitosanases are enzymes that hydrolyze chitosan, classified according to the substrate specificity towards chitosan, which act specifically on the deacetylated (D–D) bonds [133].
In recent years, many scientific papers reported the application of chitinolytic enzymes, from different microorganisms, for the hydrolysis of chitin and chitosan. Enzymes for hydrolysis can be free or immobilized in non-toxic and inert supports.
Fernandes de Assis
Gao
Ming
COS can be applied as food preservatives due to their antimicrobial activity and as functional food, mainly in prebiotics and to help the absorption of important minerals, as calcium. Antimicrobial activity of COS depends on the degree of polymerization (DP) and the degree of deacetylation (DD) as summarized in Table 1.
Inhibitory effects of COS were tested on both Gram (-) and Gram (+) bacteria, including
The proposed mechanism of antibacterial activity for COS with DP>12 was cellular lysis [139]. This would be due to the cationic charges of COS that could link to the negative charges present in the cell walls, leading to the formation of large bacterial clusters, which might block the nutrition transport across the bacterial cell and result in death of the bacteria. Highly deacetylated COS were shown to be more effective at inhibiting the growth of
It has been suggested that COS are able to pass through the bacterial cell wall and be incorporated in the cytoplasm of Gram (+) bacteria [141]. Those low molecular weight compounds can have importance in gene expression related to regulation of stress, autolysis and energy metabolism.
Chitooligosaccharides with DP 4 were demonstrated to have higher antimicrobial effect on four bacteria species (
Chitooligosaccharides can be employed as preservatives due to their antioxidative properties. Antioxidant activity of chitooligosaccharides depends on their degree of deacetylation and molecular weights [143]. It was shown that 90% deacetylated medium molecular weight COS have the highest free radical scavenging activity for DPPH, hydroxyl, superoxide and carbon centered radicals [144]. Antioxidant properties are closely related to the amino and hydroxyl groups, which can react with unstable free radicals to form stable macromolecule radicals [145,146].
According to Halden
COS were conjugated with phenolic acid (PAC-COS) to improve the antioxidant properties of the oligosaccharides in the presence of reactive oxygen species (2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH) and nitric oxide (NO)) [148]. The increase on the antioxidant activity is associated to the structure of phenolic acids and the substitutions on the aromatic ring of the side chain.
Chitooligosacharides can be considered as prebiotics because they are non-digestible food ingredients with beneficial effects on probiotic bacteria (
However, an opposite effect was shown on the population of
Chitooligosaccharides from marine species, mainly shrimps and crabs, are produced and commercialized by several companies (Table 2), such as:
Qingdao BZ-Oligo Co., Ltd: Monomers of chitosan oligosaccharides are obtained by enzymatic hydrolysis, chemical derivatization and column chromatography. The degree of polymerization is from 2 to 10.
BioCHOS: Preparation of chitooligosaccharides (CHOS) made by controlled enzymatic degradation of chitosan.
AMSBIO: Preparation of a series of chitosan-oligosaccharides from dimer to hexamer by hydrolysis of chitosan from crab shells. All oligomers are chromatographically pure, not less than 98%, confirmed by high performance liquid chromatography.
Typical oligosaccharides like FOS and GOS in particular have been widely studied for their prebiotic effects. However, a number of other non-digestible oligosaccharides (NDOs), to which less rigorous study has been so far applied, have at least indications of prebiotic potential. Those with the most accumulated evidence to date are isomalto-oligosaccharides (IMO), soybean oligosaccharides (SOS), xylo-oligosaccharides (XOS) and lactosucrose. Together with FOS, GOS, and lactulose, all of these oligosaccharides are recognized in the Japanese functional food regulation system as ingredients with beneficial health effects [152].
A great interest resides on the identification, evaluation and commercialization of new products with improved functional properties and benefic health effects such as higher ability to modulate microbiota. Arabinoxylo-oligosaccharides (AXOS), levan-type FOS, gentio-oligosaccharides (GenOS) and pectin-derived oligosaccharides (POS) are examples of these new potential products.
Isomalto-oligosaccharides are usually found as a mixture of oligosaccharides with predominantly α-(1,6)-linked glucose residues with a degree of polymerization (DP) ranging from 2–6, and oligosaccharides with a mixture of α-(1,6) and occasionally α-(1,4) glycosidic bonds such as panose (Figure 8; Table 1) [152].
Examples of structures of isomalto-oligosaccharides. Glucosyl residues are linked to maltose or isomaltose by α-(1,6) glycosidic bonds.
Isomalto-oligosaccharides, like malto-oligosaccharides, are produced using starch as the raw material. Isomalto-900, a commercial product, is produced from cornstarch and consists of isomaltose, isomaltotriose and panose. Starch dextrans are easily converted to IMO, which are the market leaders in the dietary carbohydrate sector of functional foods in Japan. However, unlike malto-oligosaccharides, there is evidence to suggest that isomalto-oligosaccharides induce a bifidogenic response [11].
IMO occur naturally in various fermented foods and sugars such as sake, soybean sauce and honey. They are a product of an enzymatic transfer reaction, using a combination of immobilized enzymes. Initially, starch is liquefied using α-amylase (EC 3.2.1.1) and pullulanase (EC 3.2.1.41), and, in a second stage, the intermediary product is processed by both β-amylase (EC 3.2.1.2) and α-glucosidase (EC 3.2.1.20). Beta-amylase first hydrolyzes the liquefied starch to maltose. The transglucosidase activity of α-glucosidase then produces isomalto-oligosaccharides mixtures which contain oligosaccharides with both α-(1,6)- and α-(1,4)-linked glucose residues (Table 2) [153].
In recent years, much research has been focused on improvement of the efficiency of IMO production by screening for new and better enzymes for high yield IMO synthesis. Efforts also have been made to develop novel processes such as synthesis of IMO from sucrose using free or immobilized dextransucrase and dextranase, and efficient conversion of maltose into IMO using immobilized transglucosidase, or using an enzyme membrane reactor [153,154].
IMO are mild in taste and relatively inexpensive to produce. These oligosaccharides have desirable physicochemical characteristics such as relatively low sweetness, low viscosity and bulking properties. IMOs have been developed to prevent dental caries, as substitute sugars for diabetics [155], or to improve the intestinal flora [152].
Several companies currently manufacture isomaltooligosaccharides, of which Showa Sangyo (Japan) is the major producer. Of the emerging prebiotic oligosaccharides, IMO are used in the largest quantities for food applications. In Japan, the volume of IMOs manufactured is estimated to be three times greater than for either FOS or GOS [152]. Among other oligosaccharides, which are widely used as food ingredients or additives [156] based on their nutritional and health benefits [157], IMO are interesting due to availability, high stability and low cost [154].
Unlike other prebiotic oligosaccharides, considerable digestion of IMO occurs during intestinal transit. A large portion of this ingredient reaches the colon and intestinal enzymes degrade the remainder, leading to a rise in blood glucose levels [154]. Thus, a part of the IMO survives gastric transit to be fermented by the intestinal microbiota [152].
Beneficial effects of IMO consumption have been reported in a few human feeding studies investigating health parameters in specific populations. IMOs stimulate bowel movement and help to decrease total cholesterol levels with an intake of 10 g/d in elderly people [158].The limited data for physiological effects showed only improved defecation pattern (frequency and stool bulk via increases in microbial biomass) and lowering of total cholesterol levels [158,159]. In conclusion, the data for the bifidogenic effects of isomalto-oligosaccharides are less consistent than for other typical oligosaccharides like inulin or oligofructose [155].
Unlike other oligosaccharides, soybean oligosaccharides are extracted directly from the raw material and do not require enzymatic manufacturing processes. These α-galactooligosaccharides include and consist of galactosyl residues linked to the glucose moiety of sucrose by α-(1,6) bonds (Figure 9,Table 1) [2].
Examples of the main soybean oligosaccharides, raffinose and stachyose, derived from sucrose, showing galactosyl residues linked to sucrose by α-(1,6) bonds.
Soybean whey, a by-product from the production of soy protein isolates and concentrates, is composed mainly of raffinose (DP 3), stachyose (DP 4) and verbascose (DP 5), as well as sucrose, glucose and fructose. The most abundant sugars are extracted from the soybean whey and concentrated to produce soybean oligosaccharide syrup (Table 2), rather than being commercially synthesized using enzymatic processes [158].
Raffinose and stachyose are resistant to digestion, since α-galactosidase activity (required to hydrolyze these carbohydrates) is not present among human digestive enzymes and, therefore, reach the colon intact, where they act as prebiotics, stimulating the growth of bifidobacteria. Apart from being acknowledged as non-digestible, human studies on the effects of these oligosaccharides are scarce. Their physiological actions appear to be similar to the other galactooligosaccharides; they are bifidogenic and promote other effects expected from this change in colon microbiota. Calpis Co. (formerly known as Calpis Food Industry Co.) produces soybean oligosaccharides in Japan [11].
Xylo-oligosaccharides (XOS) are sugar oligomers of xylose units linked by β-(1,4) linkages (Figure 10,Table 1). The number of xylose residues can vary from 2 to 10, but mainly consist of xylobiose, xylotriose and xylo-tetraose [152], which are found naturally in bamboo shoots, fruits, vegetables, milk and honey [160]. In addition to xylose residues, xylans are usually found in combination with arabinofuranosyl, glucopyranosyl uronic acid or its 4-O-methyl derivative (2- or 3-acetyl or phenolic substituents), resulting in branched XOS with diverse biological properties [153].
Partial structure of xylo-oligosaccharides (n=3-6) produced by enzymatic hydrolysis of xylan hemicelluloses, catalyzed by β-xylanases.
Their production at an industrial scale is carried out from lignocellulosic materials (LCMs). XOS can be used for several purposes, among them, food-related applications. The LCM for XOS production comes from a variety of feedstocks (from forestry, agriculture, industry or urban solid wastes) that show similarities in composition. The raw material for xylo-oligosaccharide synthesis is the polysaccharide xylan, which is extracted mainly from corncobs besides hardwoods, straws, bagasses, hulls, malt cakes and bran [160].
XOS production from LCM is not simple or economical because it depends on two treatment steps. The first step is the xylan extraction from LCM, which includes a chemical pretreatment. Although there are multiple treatments for xylan extraction (alkaline hydrolysis using NaOH, KOH, Ca(OH)2, ammonia or a mixture of bases, oxidizing agents, salts or alcohols to remove lignin or pectic substances), there is no favorite consensus among them. Once the extracted xylan is in a soluble form, the second step includes the xylanase enzymatic reaction or the hydrolytic degradation of xylan by steam, water or dilute solutions of mineral acids [160]. For the enzymatic production of XOS, xylan is enzymatically hydrolysed to xylo-oligosaccharides by endo-β-1,4-xylanases (EC 3.2.1.8) (Table 2). Enzyme complexes with controlled exo-xylanase and/or β-xylosidase activity are required, to avoid the production of xylose, which may cause inhibition effects in XOS production. For food related applications, a DP of 2–4 is the most desirable [160]. Therefore, development of efficient and economical xylanase based bioprocesses for use in XOS production is necessary. Many microorganisms well known as producers of xylanolytic enzymes may be promising for novel production processes [161].
The process yields predominantly linear β-(1,4)-linked XOS (mainly xylobiose, xylotriose and xylotetraose) as well as some oligosaccharides with branched arabinose residues. For the production of food-grade XOS, a refining step is necessary. Vacuum evaporation increases the XOS concentration and removes volatile compounds such as acetic acid and the flavours of their precursors. In order to obtain higher-purity oligosaccharide products, the monosaccharide xylose and high molecular mass carbohydrates, as well as non-saccharide components can be removed from the oligosaccharides using membrane filtration techniques, organic solvent extraction, adsorption in different materials and chromatographic separation techniques used for XOS purification. Chromatographic methods, however, are not suitable for economic reasons for large-scale production of XOS intended to be used in the food industry [153].
XOS can be metabolized by bifidobacteria and lactobacilli in pure culture. In relation to human health, XOS selectively enhanced the growth of bifidobacteria thus promoting a favorable intestinal environment [152]. XOS is a promising oligosaccharide class that stimulates increased levels of bifidobacteria to a greater extent than do FOS or other oligosaccharides [161]. However, to date well-controlled animal and human feeding studies to confirm the prebiotic activity of XOS are still scarce. While they show promise, more research is required before XOS can conclusively be claimed as prebiotics. Besides the potential prebiotic effect, immunostimulating effects, antioxidant activity, anti-allergy, anti-infection and anti-inflammatory properties were reported for XOS [162-164].
In addition to the beneficial health effects, XOS have interesting physicochemical properties; they are only moderately sweet, have an acceptable odor, are noncariogenic and low caloric, stable over a wide range of pH values (2.5–8.0), even the relatively low pH value of gastric juice, and temperatures up to 100°C. Most oligosaccharides can be hydrolyzed, resulting in the loss of nutritional and physicochemical properties at acidic pH values, when treated at high temperatures for short periods, or when submitted to prolonged storage under room conditions. These properties make them suitable for incorporation into many food products such as in combination with soymilk, soft drinks, dairy products, sweets and confectionaries [158].
XOS show a remarkable potential for practical utilization in many fields, including pharmaceuticals, feed formulations and agricultural applications. Nevertheless, their most important market developments correspond to food-related applications, however, their comparatively high production costs impair market development of these oligosaccharides, and further improvements in process technology are necessary [11].
Arabinoxylo-oligosaccharides (AXOS) are an example of a novel prebiotic dietary fiber. They can be isolated from wheat bran and consist of xylan chains with a variable substitution of arabinose side chains (Table 3) [158]. On an industrial scale, AXOS are generated through the enzymatic cleavage of AX with endoxylanases, resulting in various molecules differing in DP (between 3 and 67) and degree of substitution of arabinosyl residues [165].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Lactosucrose | \n\t\t\t4-galactosyl sucrose | \n\t\t\t[2, 156] | \n\t\t
Arabinogalactooligosaccharides | \n\t\t\tGalactan oligomers β-(1,3) or (1,6) attached to arabinofuranose residues. | \n\t\t\t[19] | \n\t\t
Arabinoxylooligosaccharides | \n\t\t\tXylan randomly attached to arabinofuranose residues by α-(1,3) or α-(1,2) linkages. | \n\t\t\t[165, 237] | \n\t\t
Arabinooligosaccharides | \n\t\t\tArabinosyl units linked by α-(1,5) bonds. | \n\t\t\t[2] | \n\t\t
Pectic oligosaccharides | \n\t\t\tLinear backbone of α-(1,4) linked D-galacturonic acid units randomly acetylated and/or methylated. | \n\t\t\t[171, 172, 238, 239] | \n\t\t
Galacturonan | \n\t\t\tLinear chain of α-(1,4) linked D-galacturonic acids | \n\t\t|
Rhamnogalacturonan | \n\t\t\tα-(1,4) linked galacturonic acid and α-(1,2) linked rhamnose units | \n\t\t|
Mannan oligosaccharides | \n\t\t\tMannose α-(1,6) linked backbone and α-(1,2) and α-(1,3) linked branches. | \n\t\t\t[176] | \n\t\t
Oligodextrans | \n\t\t\tGlucosyl units linked by α-(1,4) bonds. | \n\t\t\t[176, 240] | \n\t\t
Gentiooligosaccharides | \n\t\t\tGlucosyl units linked by β-(1,6) bonds. | \n\t\t|
Beta-glucan oligosaccharides | \n\t\t\tGlucosyl units linked by β-(1,3/1,4) or β-(1,3/1,6) bonds. | \n\t\t|
Cyclodextrins | \n\t\t\tα-(1,4) linked cyclic – glucosyl units. | \n\t\t
Novel oligosaccharides with prebiotic activities.
The fiber properties include an improvement of bowel habit and positive change of the fermentation in the colon, whereas they were also shown to possess bifidogenic properties [158]. There are indications that AXOS have an effect against type II diabetes. AXOS decrease postprandial glucose levels and insulin response, and increase postprandial ghrelin in healthy humans [156,166].
This bifidogenic effect is strongly influenced by the complexity of the AXOS molecules and decreases with increasing average DP and degree of substitution [72,166]. Genome sequence analysis reveals that several bifidobacterial strains contain genes possibly coding for enzymes involved in the debranching of side groups and in the cleavage of the xylose backbones of AXOS [72]. This kind of specialization together with the potential to degrade xylose backbones intracellularly could explain the selective growth stimulation of bifidobacteria by AXOS.
There is an increasing interest in novel molecules with prebiotic and physiological effects. Some fungi are able to synthesize levan-type FOS containing fructosyl units linked by β-(2,6) linkages (6-kestose being first in the series) (Table 1), or neolevan type FOS containing a fructosyl unit also linked by this type of linkage to a glucose (neokestose, neonystose, or neofructofuranosylnystose). Such FOS have been metabolized by different bifidobacteria strains when supplied as the sole carbon source [167].
Levan-type FOS were synthesized by acid hydrolysis of β-(2,6)-linked polymers containing a glucose at one terminus (levans), these have been produced by several microorganisms growing in sucrose-based medium [168]. The discovery of novel enzymes that synthesize β-(2,6)-linked FOS from sucrose may, however, provide a non-pollutant alternative to acid hydrolysis of levans. Because there is an existing process to produce inulin-type FOS, an enzymatic method involving the hydrolysis of levan to produce levan-FOS may be possible. However, with the lack of an available plant source of levan, as there is for inulin, it is possible to derive an enzymatic process to produce levan-type FOS from microbial levan, using levansucrase (Table 2) and endolevanases [169].
Marx
The production of levan-type FOS has not reached industrial levels [171], despite several reports demonstrating their potential applications as food and feed additives in agriculture as well as their pharmaceutical applications.
Pectic oligosaccharides (POS) (Table 3) are obtained by pectin depolymerization. Pectins are ramified heteropolymers made up of a linear backbone of α-(1,4)-linked D-galacturonic acid units (which can be randomly acetylated and/or methylated).
POS have been proposed as a new class of prebiotics capable of exerting a number of health-promoting effects. Among these are protection of colonic cells against pathogenic microorganisms [172], stimulation of apoptosis of human colonic adenocarcinoma cells [173] and
Gentio-oligosaccharides (GenOS) consist of 2–5 glucose residues linked by β-(1,6) glycosidic linkages (Table 3). These oligosaccharides are not hydrolysed in the stomach or small intestine and therefore reach the colon intact, thus fulfilling a criterion of a prebiotic [11]. GenOS were further reported to possess bifidogenic activity [153]. GenOS are usually produced from glucose syrup by enzymatic transglucosylation or by biocatalytic glycosylation with cultured cells. Despite the prebiotic potential of GenOS, research on the novel production of GenOS is sparse. Gentio-oligosaccharides are produced in Japan by Nihon Shokuhin Kako [11].
Function and application of chitooligosacharides frequently depend on their size, and, therefore, the degrees of polymerization and acetylation. Substrate-enzyme synergisms determine the molecular weight of the generated COS. Gutierrez-Román
Further studies must be focused on the action of the enzymes on substrates with different degrees of polymerization and acetylation and N-acetylation pattern to improve the comprehension of that synergism. In addition, researches involving synergism of non-catalytic binding proteins and hydrolytic enzymes should be developed in order to increase the understanding of oligomers syntheses [127]. Consequently, to produce size-specific chitooligosaccharides by enzymatic hydrolysis, further studies on genetic modification are necessary to overproduce enzymes and non-catalytic binding proteins, which will have a great impact on the quality of oligomers obtained and on the productivity of industrial processes.
Another important challenge in the development of biotechnological processes that employ agro-food industry residues as raw material is the direct fermentation of those raw materials. Obviously, direct fermentation of raw materials is closely related with the aforementioned aspects, since fermentative processes involve microbial growth and enzymatic hydrolysis, and process conditions that in many cases are different from physiological conditions. Moreover, it is important to give attention to screening of new enzymes from extremophile microorganisms, which usually catalyze reactions under non-physiological conditions such as high salinity, high temperature and low water activity [175].
As important part of the biotechnological process, bioreactors and enzyme (free or immobilized) are essential and need special attention to improve yields and productivities. Free enzymes in batch systems are the most conventional technology employed in the production of oligosaccharides by enzymatic hydrolysis. However, it has several important drawbacks, because enzymes are unstable, can be employed once and accumulation of products usually reduces their activity. These drawbacks are related directly to the quality of the product and the yield of the process. Development of novel technologies in order to solve those snags employing immobilized enzymes in column reactor and membrane systems have been studied. Column reactor packing with immobilized enzymes allows continuous production of oligosaccharides and has important advantages, such as increased operational stability of the enzyme and reduced accumulation which otherwise could lead to enzyme inhibition. The poorer affinity of immobilized enzymes is the main disadvantage of the application of column reactors at industrial scale. Studies should be directed towards the improvement of enzyme-support affinity. Membrane reactors are considered a new and attractive technology to produce oligosaccharides, in which enzymes are confined in the reaction side and continuously reused, with obvious implications for the efficiency and economy of the process. Low-cost and low-energy consumption are other important advantages to increase its utilization. The main limitation for industrial application of membrane reactors are fouling and polarization phenomena, which decrease considerably permeate flux, containing the produced oligosaccharides [176]. The main challenge to be studied in order to implement this technology advantageously in the industry is how to reduce the effect of these problems without affecting the stability of enzymes.
The use of wood shavings in wine production has been documented in France since the nineteenth century. It was an unusual, but well-known, practice to improve the sensory characteristics of some wines using untoasted chips of oak wood or service trees [1]. The modern use of wood fragments in winemaking began in new winemaking countries in the early 1960s [2]. In 1993, the United States regulated the use of such products in oenology. In Europe, their use was opposed until the early 2000s, but finally in 2006, Regulation (EC) No. 1507/2006 of the Commission authorized the use of pieces of oak wood in oenology, enabling European producers to compete in a rapidly evolving world market. The new EU Delegated Regulation 2019/934 [3] currently regulates the use of oak wood chips in oenology, which are used for several technological purposes. The main objective is the release of desirable compounds, mainly aromas and polyphenolics, from the wood fragments into the wine during aging.
The main reason supporting the increased use of wood chips in wine production was essentially economic. The cost of wood chips is considerably lower than that of wooden casks. The production of wood fragments involves industrial-type technologies and therefore, is much cheaper than the artisanal processing of barrels. In addition, the wood, although from the same botanical species, in the case of barrels, is obtained from the most valuable part of the trunk, whereas woody fragments are usually recovered from less valuable parts or remnants of
Nowadays, wood fragments represent an opportunity for wine producers to diversify their product in order to satisfy different market needs. From a technological point of view, the oenologist can choose the size of the wood pieces, the duration of the contact with the wine and the moment of application.
On the other hand, the same reasons that supported the spread of wood chips in wine production also prevented its acceptance from a regulatory point of view. Indeed, as mentioned above, there is a cost-reduction associated with the use of oak wood chips, obtained by giving a woody touch to the wine without the need to use barrels; however, without proper regulation, this could lead to fraud. If such wine is offered as barrel-aged wine [4, 5], the false use of quality indications on its label represents counterfeiting, which is detrimental to consumers and legitimate producers. Therefore, the challenge to distinguish between wines obtained using one refinement technique or another is particularly crucial, even if complicated by the multiplicity of variables involved. However, it is equally clear that, due to the need of control for both consumer protection and quality assessment, the continuous improvement of investigation methods is essential, either analytical or sensory, that allow distinguishing wines aged in barrels from those treated with chips or alternative woods.
The current European legislation stipulates that the wood used in winemaking must come exclusively from the
The oak wood chips employed for oenological use are small pieces of wood with dimensions ranging from a minimum of 2 mm (sometimes called granulates, tabacs or wood rice) up to about 20 mm (sometimes called shavings,
Currently, the market offers numerous alternatives to classic wood fragments. They are frequently larger products than typical chips, able to simulate aging in barrels more effectively. Commercially, they are called cubes, beans, blocks, dominoes, segments and so on. Xoakers are wooden spheres of small dimensions, measuring a few centimeters in diameter. The doses are variable, generally between 2 and 4 g/L. The infusion time varies from 1 to 6 months.
Oak staves, ministaves, and sticks are wooden slats or cylinders of variable size from a few centimeters to a meter long, width range of 25–75 mm and a thickness variable between 7 and 18/22 mm. Commercially, they are denominated in a variety of ways, but all these products share the same oenological objective, which is to optimally simulate aging in barrel. The recommended doses for the smaller ones are 1–5 g/L for about 6–12 months of contact time. Sometimes doses are reported as wood area/wine volume.
Products with dimensions less than 2 mm are not permitted by European legislation [3] but can be used by New World manufacturers and take the commercial name of dust or flour. The small size of the wood considerably increases the exchange surface with the wine and consequently, the extraction processes of aromatic compounds and tannins are very rapid (15 days to 4 months). The cost of the treatment is therefore extremely low due to the low cost of the product and the limited quantities that are used. Oak powders have the advantage of being able to be pumped together with the wine during racking operations; however, it is much more difficult to remove from wine than chips or staves. The doses vary between 0.5 and 2 g/L of wine.
All these products can be used at different stages of winemaking and for various purposes. Generally, untoasted fresh chips or low toasted wood chips are used in the early stages of winemaking in order to allow color stabilization improving the anthocyanin extraction in young wines and their color characteristics during wine stabilization [9]. Toasted products can be used both during the alcoholic fermentation and after the end of malolactic fermentation.
The use of alternative products assumes that a huge array of variables must be considered including the type of wood, the size and shape of fragments, the mode of wood seasoning, the grade of toasting, the moment of use during winemaking, duration and the timing of contact as well as the interaction with yeasts and bacteria involved in winemaking. The main technological variables are examined below.
Commonly, the wood used for alternative products is obtained from remnants of the barrel-making process, especially in the production of granulates or chips. This is not a negligible part of oak wood, but almost 50–75% of the total production, depending on the method used for barrel stave production, that is, traditional via splitting or by sawdust. Oak wood is otherwise obtained from trees with small diameters or presenting some physical defects [10]. Sometimes, for example, for high-quality alternative staves, the wood is the same as that used to produce barrels. In all cases, to obtain a high-quality product, it is necessary to pay particular attention to the seasoning phases that should occur in the best possible conditions [1]. Seasoning is a fundamental process useful in eliminating excess water present in the wood from 70% to about 14–18% [11]; it can be carried out naturally, alternatively, by forced drying.
During natural seasoning, the wooden planks are stacked outdoors in the open air for a variable period, which depends on the thickness, and ranges from about 2–3 years. Slats are periodically moistened to remove, via leaching, the excess astringent and bitter compounds, such as tannins and coumarins, present in the wood [12, 13]. Furthermore, the presence of unpleasant compounds is attenuated, primarily
Artificial seasoning allows cost containment and a considerable reduction in processing time. However, natural seasoning leads to a greater accumulation of odorous compounds in the wood, in particular, volatile phenols, phenolic aldehydes, furanic compounds, and
After seasoning, it is necessary to eliminate residual sapwood and bark that have a very different composition to heartwood, which is the most precious part of the wood. Oak wood is then processed to reduce it to the most appropriate size and is eventually toasted. During toasting, numerous transformations take place such as, the partial degradation of the wood polyosides that leads, in turn, to the formation of numerous odorous compounds. At the same time, a large portion of the tannins undergoes degradation, with the extent depending upon the degree of toasting. Unlike the production of barrels, the toasting of alternative products is, generally, an easy, automatic process. The technological solutions for their toasting are varied and include: direct contact of the pieces of wood with a suitably heated surface; by means of a suitably heated air jet; by irradiation with IR rays, which does not allow deep toasting of the pieces; by direct contact with a flame, used almost exclusively for the production of alternative staves. Two main benefits must be considered: the first is reducing production costs; the second is standardization in terms of quality. The toasting degree of the alternative products follows that for wooden barrels; therefore, they can be distinguished as untoasted or with a light, medium or high (heavy) toasting level. However, this classification does not represent an absolute reference as the technologies used by individual companies may differ considerably [19].
From an oenological point of view, the oak heartwood is the wood of major interest. Its chemical composition includes three large groups of compounds. The first one consists of certain polymers constituting the cell wall and the median lamella of the vegetal cells with supporting functions. The second group is composed of several extractable substances accumulated during the natural transformation from sapwood to heartwood, as well as tannin deposits which protect against plant parasites. The third group includes, in smaller quantities, several compound residues of cellular metabolism: amino acids, fatty acids, terpene compounds, carotenoids, and various minerals [20, 21].
From a quantitative point of view, the main components of oak heartwood are cellulose (40–45% of dry weight), hemicellulose (20–25%) and lignin (25–30%) and, overall, they represent by weight, the predominant portion of the wood. These polymers form a three-dimensional structure, trapping cellulose in an insoluble and rigid matrix of lignin and hemicellulose, which gives the wood its typical technological characteristics.
Chemically, cellulose is a crystalline homopolymer consisting of units of glucose 1,4-β-bonded, which has an average molecular weight of 106 Da corresponding to 10,000–15,000 monosaccharide units. Hemicellulose is a complex polymer that may contain pentoses (β-d-xylose, α-l-arabinose), hexoses (β-d-mannose, β-d-glucose, α-d-galactose), and uronic acids [22]. Structurally, it has two roles: binding cellulose microfibers and strengthening the cell wall. It is worth noting that both the concentration and structure of this polymer differ between sapwood and wood. Finally, lignin, which from a structural point of view is a
Finally, both the rate of growth and botanical origin affect strongly the chemical-physical characteristics of the wood. Slow growth leads to fine grains, less dense wood, which is of greater resilience and, most of all, richer in extractable compounds, whereas rapid growth leads to the formation of medium or coarse grain woods. As regards botanical origin the main differences concern the tannin content, generally higher in the heartwood of European origin and the volatile compounds (lactones, norisoprenoids, sesquiterpenes, and fatty acids), usually more abundant in
β-methyl-γ-octalactone is included among the minority aromatic compounds, but it has a crucial role from a sensory point of view. This is a natural lactone present in fresh oak wood, and it is characterized by intense notes of coconut, celery, and pastry with a very low perception threshold. Also called whiskey lactone or oak lactone, because it was discovered in the 1970s for the first time in whiskey and shortly thereafter in the oak wood used for their processing [24, 25], oak lactone is formed from the cyclization of 3-methyl-4-hydroxyoctanoic acid. This compound is present in oak wood as a glycoconjugate precursor namely, galloylglucoside, glucoside, and a rutinoside derivative [26, 27] and can undergo hydrolysis during both seasoning and toasting operations or during the maturation of the wine in contact with the oak wood.
From a structural point of view, oak lactone is a molecule with two chiral carbons, therefore, four different optical configurations are possible. Only two stereoisomers of oak lactone are present in oak wood [28], the “
Generally, this compound is more abundant in American oak wood. A recent work showed that wines macerated with
Among the aromatic compounds from fresh oak wood that have a significant impact on the aroma of wine can be included eugenol, which is characterized by typical clove notes and is present in small quantities, especially in sapwood [34]. Another important group of naturally occurring compounds is that of norisoprenoids [35]. These compounds originate from the degradation of carotenoids and xanthophylls present in the wood. Some of them have very low perception thresholds and perfumes that vary from floral to balsamic (see Section 3.4).
The degradation of wood polymers under an inert atmosphere proceeds gradually following the increase of temperature [36]. The decomposition of hemicellulose and cellulose takes place at 200–380°C and 250–380°C, respectively, while lignin decomposition occurs over the range of 180–900°C. Moreover in normal cooperage conditions, the degradation of cellulose occurs with great difficulty and the sensory impact of its derivatives remains negligible [22]. On the contrary, hemicellulose is more susceptible to hydrolysis, which can occur during both toasting and wine aging, and leads to an increase in the total content of galactose, fructose or xylose [37], up to a few hundred mg/L. From a microbiological point of view, this aspect should be considered carefully for the development of undesired microflora in wines, taking into account the ability of some spoilage microorganism, namely
Other compounds, namely maltol and cyclotene, originating from hemicellulose degradation [22], are characterized by specific caramel notes. Like furanic aldehydes, they have a limited impact on empyreumatic notes of wine aged using oak wood, because of their high perception threshold. Sugar condensation products such as DDMP (2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one), HDMF (4-hydroxy-2,5- dimethylfuran-3(2H)-one) and DHM (dihydromaltol), derived from glucose and proline condensation, seem to have a greater impact on the toasty/caramel aroma [40].
Finally, the thermodegradation of lignin leads to the formation of several key aromatic compounds including aromatic hydrocarbons, phenols (mainly monomethoxylated and dimethoxylated derivatives), aromatic aldehydes (benzoic aldehydes), and syringyl-derived compounds. Various factors such as the moisture of the wood, the intensity of the heat applied, the presence of other polymers such as cellulose can influence the chemical yield of these reactions [41]. Specially, the toasting intensity is the factor that most influences the final composition of these compounds in wine. Low/medium levels of heating lead to the formation of cinnamic and benzoic aldehydes as synapic aldehyde, coniferyl aldehyde, vanillin, and siringaldehyde. Among these, vanillin has an important aromatic impact thanks to its recognizable scent and low perception threshold [39]. More intense toasting levels lead to the formation of volatile phenols such as phenol, cresol isomers, guaiacol, 4-methylguaiacol, eugenol, isoeugenol and propiovanillone, some of them characterized by a low perception threshold and clear spiced or smoky notes.
Finally, some heterocyclic compounds present in small quantities, such as pyrazine, pyrrole pyridine, and triazole derivatives have been identified in toasted wood extracts. These compounds could be generated by Maillard’s reaction during the toasting operations [42].
The type of alternative wood has an important influence on the diffusion kinetics of aromatic compounds. Generally volatile compound accumulation is faster using wood chips than staves, on the other hand, staves lead to a greater accumulation of aromas, in all cases, the extraction seems to be complete after 3–12 months of aging [10, 43].
The botanical origin of wood has great importance in defining the transfer of aromatic compounds namely, oak lactone to wine. Wines aged in contact with American oak chips showed a significant increase of
The aging time was related to a higher content of esters [44]; the type of wood pieces was correlated to
The accumulation of phenols depends on the degree of toasting but, in general, a higher accumulation of these compounds occurs in wines aged with staves compared with those aged with chips [45]. For guaiacol, 4-methylguaiacol and eugenol, the maximum accumulation has been registered between 6 and 12 months.
The main variations during wine aging involve furan aldehydes; these changes are certainly decisive for wine quality. During the first months of storage, a high accumulation of furan aldehydes is observed [45], more remarkable in aging with staves than with chips; then their content decreases sharply, similar to that occurring in wines aged in
Yeasts can also transform furfural to 2-furanmethanethiol (2-FMT), through the addition of hydrogen sulfide present during fermentation to furfural [49]. 2-FMT, with a very low perception threshold (0.4 ng/L) and its distinguishable odor of coffee [50], is the key aroma compound of the
The “extractable fraction” of wood represents up to 10–15% of dry heartwood. Certainly, ellagitannins are the most abundant components in this fraction and, together with other compounds, are the source of many of the interesting sensory characteristics found in aged wines [53]. Eight ellagitannins have been identified in traditional oak species: castalagin, vescalagin, granidin, and roburins (A, B, C, D, and E), with the two most abundant compounds being the stereoisomers, vescalagin and castalagin [53, 54, 55]. Ellagitannins are transferred to the wine during aging, contributing to sensations of bitterness and astringency and behaving as antioxidants due to their capacity to consume oxygen [15, 53, 54, 55]. Moreover, ellagitannins directly affect wine color via reactions with anthocyanins forming red orange anthocyanin-ellagitannin complexes that are much more stable over time than free anthocyanins [55]. They often also occur in association with flavonoids to form flavano-ellagitannin derivatives (such as acutissimin A and acutissimin B) detected in aged wine and are also involved in tannin condensation [54]. Variation in ellagitannin concentration in the same wood, due to the different cooperage processes has been reported in various papers [53]; focusing on ellagitannin and alternative products, a recent study [56] performed with model wine showed that French oak chips released significantly higher amounts of ellagitannins than American oak chips at any toasting level. Their release by oak chips decreased as the toasting level increased in the French oak but this trend was not so clear in American oak.
Oxidation, condensation and polymerization reactions, in which phenolic compounds are involved, are oxygen dependent. During the aging of the wine in barrels, oxygen intake may promote, disappearance of reduction off-flavors and reduction of vegetal characteristics, but also color intensity and stabilization. This process, in barrels, is not a controlled process, but depends on wood characteristics. On the contrary, a monitored oxygenation process in stainless steel tanks can control the changes in the phenolic structure and aroma of the wine by managing oxygen-requiring reactions [57, 58].
Oxygenation of wine, which is defined as the diffusion of air or oxygen into the wine, is an authorized oenological practice in the International Code of Oenological Practices of the OIV [59]. Micro-oxygenation (MOX), consisting of dispensing micro quantities of oxygen in a controlled way, was developed in France by Patrick Ducournau at the beginning of the 1990s, then Ducournau and Laplace registered a patent for the MOX method [60, 61]. Several researches have experimented MOX combined with the application of oak alternative products with the purpose to simulate the evolution and stabilization of the phenolic compounds that spontaneously takes place in barrel.
The formation of acetaldehyde from ethanol oxidation during wine MOX favors the creation of ethyl bridges between flavanols and between flavanols and anthocyanins leading to an increase of both color intensity and color stability [62]. Ellagitannins contributes to the formation of ethylidene-bridged anthocyanin-tannin adducts through the formation of hydroperoxy radicals [63]. Moreover, MOX generally favors the formation of pyranoanthocyanins rising from the reaction of anthocyanins with small molecules, namely acetaldehyde. These compounds are likely to contribute to the red/orange hues observed in red wines during aging [64]. Acetaldehyde can also form bridges between tannin molecules, creating macromolecular structures that precipitate, leading to a decrease in astringency [65].
In general, MOX in combination with ellagitannins increased color intensity, even after 5 months of bottle aging due to increase of polymeric pigments including ethylidene-bridged compounds. These compounds contributed to the red and violet color range, but reduced hue levels, due to larger contributions to the 520 nm range [66] as shown for the treatment MOX with added tannin.
The oxygen consumption rate was clearly related to the level of released ellagitannins. Therefore, oak chips should be chosen considering their potential to release ellagitannins, not only because they can have a direct impact on the flavor and body of the wine, but also as they can protect against oxidation. Moreover, the origin and size of the oak chips seem to influence results when their addition is combined with MOX technique. The effect of American, French and Spanish oak chips or staves on in combination with MOX during red wine aging was researched; wine treated with staves (larger pieces of wood) and also aged with French oak products consumed more oxygen [67]. Finally, grape variety and especially MOX had more influence on phenolic composition and wine color than the type of oak chips which did not modify the chromatic characteristics of the red wines [68].
Various isoprenoid compounds and derivatives have been isolated and described in oak wood. Among them terpenes are compounds with a very low perception threshold and remarkable olfactory pleasantness; however their contribution of wood to wine is rather limited [69]. On the contrary, the presence of carotenoids is an important factor to consider for barrel production. The content of carotenoids in oak wood is found to be generally low and considerably variable between samples, depending mainly on the color of the piece of wood. Pinkish woods are mostly considered for barrel making being significantly richer in carotenoids than other colored woods. In particular, the molecules responsible for the pinkish hue of woods are found to be principally β-carotene and lutein [70]. Carotenoid compounds are highly sensitive to oxygen, light and temperature.
Pyrolysis/Gas Chromatography/Mass Spectrometry (PY/GC/MS) used on samples of French oak, to simulate the heating of barrels demonstrated that the thermal degradation products obtained after pyrolysis of β-carotene and lutein respectively were essentially norisoprenoids and sesquiterpenes [71]. During the natural seasoning the wood barrels are exposed to light and oxidation, then to heat during toasting and new aromatic compounds could be produced. With regard the norisoprenoids, over 30 different highly odorous compounds derived from the degradation of carotenoids, have been highlighted in oak wood, among which the main ones are 3-oxo-a-ionol, and dehydrovomifoliol [35]. American oak wood seems to be richer in norisoprenoids than that of European origin, while numerous compounds are common to both oak and grapes.
Finally, several pyrazines and pyridine derivatives have been detected in toasted oak wood [72]. Among them 2,5-disubstituted pyrazines seem to be responsible for rancid butter off-flavor [73]. Moreover 2-methoxy-3,5-dimethylpyrazine is linked to “corky,” potato, green hazelnut, and dusty odor [74]. However this compound, synthesized by some proteobacteria, degrades at temperatures above 220° C, consequently the wood toasting reduces significantly its content.
Other extractable compounds present in smaller quantities in oak wood are amino acids, fatty acids and minerals.
Several research studies have highlighted the effects of the application of wood fragments on the sensory profile of wines. Some findings on the topic are reported below.
Generally, the oak-chip treatment favors the polymerization of anthocyanins and tannins, leading to a reduction of monomers in wines. In a research involving two Italian red wines, Aglianico and Montepulciano, after 1 year of aging, the content of polymeric phenols in both red wines was about 40% higher in oak-treated samples compared with the control wines. This effect, however, strongly depends on grape variety and on the polyphenolic profile of each cultivar. The same oak chip-treated samples showed attenuation of floral and fruity descriptors and the introduction of oak notes (woody, vanilla, spicy notes, and black pepper), accompanied by a higher astringency. After 1 year of aging, the flavor complexity decreased, especially the spicy notes and astringency, which were even more reduced in the oak-treated samples than in the control wines [75].
The sensory profile of wine also depends on the phase of the winemaking process at which the oak chips are added, as well as on the oak chip dose. A study on the red wine Bobal [76] showed that the wines with oak wood chips added during alcoholic fermentation had a similar sensory profile to control wines with olfactory attributes of red fruits, liquorice, pepper, leather, tobacco, and cassis, but with some woody notes. On the other hand, wines with oak chips added during malolactic fermentation showed higher intensities for the oak descriptors than wines with the oak chips added when the malolactic fermentation had finished. The intensity of woody attributes was higher when the chips were added in higher doses (6 g/L).
Another experiment with white wines, Verdejo, showed the different effects of medium-toasted oak chips added during the alcoholic fermentation or aging stage [75]. With respect to the control (no chips were added), oak-treated wines showed a decrease of the descriptors fresh, green apple, fruity, tropical fruit, and citric and higher intensities for “ripe fruit” and “sweet” and for new attributes like coconut, sweet spices, woody (oak), and toasty in the oak chip-treated wines. Specifically, the wines with oak chips added during the alcoholic fermentation presented a lower content of volatile oak-extractable compounds, thus intensity of wood-related sensory attributes, but higher concentrations of fermentative volatile substances than the new wines aged with oak chip. The toasting status of oak chips (toasted or not toasted) seemed to be more relevant than the origin of oak in a study carried out on Chardonnay wine [77]. The differences highlighted among wines with added oak chips of different origin, did not influence the preference of the panel. On the other hand, the level of toasting was more important than the origin of the oak chips (German or French) [78] . Finally, the quantity of oak chips can have greater impact than the origin of the oak [79]. The sensory profile of the white wines
Nevertheless, other research results have shown sensory differences attributed to the origin of the oak chips [31]. The wines (Romanian red wines Fetească neagră) aged in contact with American oak chips had a higher intensity of vanilla, toasty and cacao aromas compared with the wines aged using French oak chips, which had a higher intensity of smoky, licorice, and toasty aromas. The degree of toasting of the wood chips or staves also influenced aromas in the same Romanian red wine [44]. A woody attribute was more evident in wines aged with oak pieces with a low degree of toasting, whereas medium plus toasted wood increased the fruity aroma descriptors.
With the aim of simulating the effect of an oak barrel, the wood pieces can be added to wine in combination with micro-oxygenation [80]. This technique (oak chips or staves combined with micro-oxygenation) can produce wines with sensory characteristics very similar to those of products aged in new American and French oak barrels for 6 months [57].
As previously described, the quantity of oak chips, their dimensions and shape, their degree of toasting, contact time, and the stage of the winemaking process of their application can influence the sensory characteristics of the wine in numerous ways. Moreover, traditional refinement in wooden containers can lead to different results based on factors such as the time of contact, the use of new woods or used barrels, the period and frequency of an eventual
From a sensory point of view, wines refined with chips in steel containers are not clearly different from those long preserved in new barrels [81]. On the other hand, young wines made with chips are almost sensorially indistinguishable from those stored in new barrels for short periods (about 3 months); both are characterized by light
The sensory differences between wines aged in wood barrels or with oak wood fragments do not always reflect significant differences regarding consumer preference [83]. In a survey on consumer preferences, a large disparity of preferences was found among the participants that traditionally consume quality wines. A large proportion of respondents (55%) said that they would not buy wines produced using oak wood chips, whereas others declared that they would buy them only if, after tasting they had perceived the same quality as the wines in wood barrels. However, young people seemed to be less traditional and more open to buy a wine produced using oak wood fragments. Another online survey [84] involving Australian wine consumers reached similar conclusions.
Finally, the use of oak wood fragments could be an interesting alternative to barrels in emerging wine countries, such as Mexico [85] or Brazil [86], due to their lower costs. Nevertheless, before using oak wood in winemaking, local producers should investigate the preferences of their potential consumers.
The challenge of explaining the sensory differences described previously from a chemical point of view, is not easy. Considerable works have addressed the chemical characterization of wines aged with alternative products. However, only some of these studies have directly compared the composition of a barrel-aged wine and that of a wine in contact with wood oak fragments [45, 87, 88, 89, 90, 91]. Nevertheless, it is equally clear that, because of the need of control for consumer protection and quality assessment, it is essential to develop methods of investigation that allow distinguishing wines arising from barrel aging from those that used alternative woods. To our knowledge, the main techniques that have been used so far for this purpose are: (i) methods examining differences in phenolic composition (based on High Performance Liquid Chromatography (HPLC) or on classical phenolics determination) and color analyses; (ii) chromatographic techniques investigating.
Variances in xylovolatiles and other Volatile Organic Compounds (VOCs), mostly Gas chromatography (GC) and GC–Mass Spectrometry-based (GC-MS); (iii) infrared spectroscopy (IR) for discriminating wines through an overall chemometric approach, mainly through NIR (near infrared) and MIR (Mid infrared) spectroscopy; and (iv) Nuclear Magnetic Resonance (NMR)-based methods. Most of the following research work is based on studies carried out by coupling 2 or more of the abovementioned techniques, and treating the composite data sets through multivariate statistical analyses [5].
A primary work in 2004 analyzed changes in phenolic compounds, phenolic acids, aldehydes, and the color of wine aged for 5 months in order to determine the influence of the type of aging and oak wood origin used for storage. A discriminant analysis was performed with the aging system as the discriminant factor, using over 66 samples. Wines aged in wood barrels differed considerably in their characteristics with respect to wines aged with wood chips. Based on the obtained model, 94 and 83% of the samples aged in barrel and chips, respectively, were correctly assigned [88]. A further, comprehensive study was carried out to discriminate wine aged in wood barrels from those aged with alternative products, both during the wood contact period and bottling stage [89]. During the first 6 months of aging, wines treated with wood staves obtained characteristics that were halfway between wines with chips and those aged in wood barrels [89]. However, as the wood contact period increased so did the differences between wines stored in traditional and alternative systems (staves or chips): after a 2-year bottling period, the wines from the three systems became unique enough to tell them apart. Discriminant analysis revealed the most meaningful variables: the yellow color component, anthocyanins (cyanidin-3-glucoside, vitisin A and sum of
The factorial analysis performed during the investigation of both phenolic and sensory profile of red wines aged in wood barrels (French and American) and wines aged with oak wood chips, [81] highlighted several differences; wines aged with wood chips showed characteristics closer to the wines aged in wood barrels for 3 months. Moreover, total and polymeric anthocyanins, together with acetylated and glucoside anthocyanins and pigments from the direct condensation of anthocyanin flavonol, seem to be the main variables able to differentiate wines [81]. Authors also pointed out the strong effect of grape variety on the discriminant variables associated with “alternative” or “traditional” wines.
A recent study [91], aimed to characterize the flavonoid and non-flavonoid phenolic composition of wines in contact with wood barrels, chips and staves during a 12-month aging period has hypothesized that the effect of wood on the phenolic composition was mostly associated with the original and intrinsic characteristics of each grape variety. Therefore, this work concluded that the extraction of phenolic compounds from oak wood during wine aging is closely related to the wood format, to grape variety and aging time. Consistent with papers previously presented, the study confirmed that the final effect of wood on wine is not related only to the transference of polyphenols from wood, but also to structural modifications of grape polyphenols.
As a matter of fact, GC-MS is successfully used for the characterization and quantitative determination of volatile and semi-volatile compounds directly issued from oak wood [92, 93].
Among the many research studies using GC-MS in order to distinguish wines aged with alternative products or barrels, the work presented by Triacca et al. [94] stands out for the number of samples analyzed. A database made up of 352 new barrel wines, 665 used barrel wines and 600 chip wines, was created in order to verify compliance with laws and regulations prohibiting the use of chips in Switzerland. Wood-related volatiles (xylovolatiles) were elaborated using chemometrics techniques (logistic regression analysis). The authors were able to assign new unknown samples, with good certainty, to the chips or barrel group [94].
A research study carried out in 2008 [95] reported the influence on aroma compounds of adding oak wood chips either in stainless steel tanks or in used barrels, comparing these wines with those aged in new barrels. Both the size of the oak chips and the contact time were considered. To separate the samples according to wood format, three discriminant functions were obtained (81.5% correct classification). Wines in new wood barrels were separated from wines with wood chips, and lactones and 5-methylfurfural were the variables with the highest discriminant power. In a recent comprehensive study [90], 75 volatile compounds were determined by applying GC-MS and flame ionization detection (GC-FID) to a wide set of wines with differing aging processes. The authors found that compounds directly related to wood have greater discriminative power for separating wines aged in barrels from those macerated with oak fragments, but no single compound permits flawless classification. Therefore, they studied the overall effect of the addition of oak fragments on a set of 231 samples and compared them to those same wines aged in oak barrels. Thus, they developed a set of criteria that enables distinguishing, with a high degree of accuracy. The application of these criteria allowed the correct classification in over 90% of cases. It was found that out of the 75 analyzed compounds, those which best enable discrimination are the following: oak lactone isomers, vanillin, acetovanillone, syringaldehyde, furfural, furfuryl alcohol, 5-methylfurfural, 5-hydroxymethylfurfural, eugenol, methyl vanillate, and ethyl vanillate. Vanillin, acetovanillone, and syringaldehyde are the compounds that were present in higher concentrations in wines fermented or macerated with wood fragments than in wines aged in barrels. Eugenol (significantly higher) and oak lactone isomers are the compounds that explain the variance in wines aged in barrels. The authors also point out that the extraction of wood-derived compounds is affected by many factors such as the age of the barrel, the application during fermentation or maceration and the dose. Nevertheless, the vanillin + acetovanillone/eugenol ratio was an essential marker for discrimination.
A more recent study [96] focused on the characterization of xylovolatile aromatic compounds using GC-MS of wines aged in barrels and those produced using oak chips. Approximately 200 Italian wines aged using oak chips or wood barrels were analyzed and 60 xylovolatile compounds were identified. Wines aged in barrels had a higher concentration of ethylvanillate, 4-ethylphenols, eugenol and whiskey-lactones than wines aged with chips, which were characterized by a generally higher concentration of furanic compounds and hydroxybenzaldehyde derivatives. The presence of 4-ethylphenols at higher concentrations in barrel-aged wines indicated that there is still, in general, a higher risk of contamination from
On the other hand, other work has demonstrated that discrimination based on VOCs is not always easy and generalized patterns are hard to establish [97]. The analytical profile of the wood-related volatiles would be expected to exhibit large variations, precluding the detection of a generalized pattern in several cases. Moreover, the aging of red and white wines would certainly follow quite different evolution routes, in terms of the enrichment in wood-related volatiles.
An innovative approach recently proposed in some papers [32, 45] couples VOC analyses with other analytic techniques to overcome the problems described above. Indeed, most previous studies investigating the influence of the type and length of the aging process have dealt with a particular subgroup of compounds (volatile or phenolic), which has recently been considered to be a limiting condition to obtain a more comprehensive view of the subject [45]. Therefore, a study carried out in 2008 on Spanish wines [45] followed the evolution of both aromatic and phenolic composition of wine during the contact time with oak wood: chips and staves, with and without micro-oxygenation. These aging procedures were compared with the traditional oak barrel aging method. Two canonical discriminant analyses were carried out to classify the different treatments based on the volatile compounds from oak wood and low-molecular weight phenols. A good separation was achieved between the three treatments (chips, staves and barrels) for both groups of compounds. In the case of VOCs, 100% of cases were correctly classified. Wines aged in barrels were correlated with a high concentration of 5-hydroxymethylfurfural and 5-methylfurfural; wines in contact with staves were correlated with a high content of vanillin and
The main aim of another research was to evaluate the same wine after 10 years in bottles when aged in barrels and when treated with alternative products and oxygen, by means of volatile compound quantitation and color analyses [32]. Overall, the traditionally aged wines suffered a smaller decrease in color intensity, hue, significance of reds and blues, followed by wines treated with staves + MOX and chips + MOX. Furthermore, the highest concentration of
It is worth noting that the GC-MS technique and VOCs analyses have been used in several studies on wood alternatives, although without direct comparison with barrel aging, investigating various technological implications: the impact of time of the addition of chips during winemaking [98, 99]; the effect of wood toasting degree and contact time with oak fragments [31, 44]; and the geographical origin of oak wood from which alternative products are issued [77, 100].
In the last decade, vibrational spectroscopy, namely infrared-based techniques (IR), supported by chemometric methods, was found to be a powerful technique because of its widespread use in analytical laboratories, its versatility and low economic impact. Moreover, IR technology requires minimal sample processing prior to analysis [5].
Certainly, IR spectroscopy coupled with multivariate data analysis has been used for the determination of oak volatile compounds [101, 102, 103] and for classifying barrels [104]. Subsequently, in recent years, this method has been proposed for discriminating wines aged in different types of wood containers and for different time periods [96, 105, 106], taking advantage on PLS-based calibration between GC-MS and near infrared spectroscopy (NIR).
The first publication appeared in 2012 [107], which investigated two different levels of information on fusion of NIR spectra and midinfrared (MIR) spectra from red wines aged in different ways. A total of 96 red wines, including wines aged in oak barrels, wines aged in stainless steel tanks with oak chips and without, were analyzed. Discriminant models of the three different aged wines were established, and the FDA method was applied to build the classification models of three different aged wines using the NIR, MIR and the merged spectra, reaching up to 98% correct classification with the latter. The results suggest that the spectral fusion of NIR and MIR is a promising technology for discriminating different aged wines.
A recent paper aimed to identify if spectroscopic techniques allow discriminating wines aged with alternative oak products (chips and staves) from different oak woods (American, French and Spanish) and floating micro-oxygenation (20 μg/L), compared with those aged in barrels, after 10 years of bottling [108]. The spectral information and analysis were performed in an FTIR-ATR (Fourier-transform IR-Attenuated Total Reflection). The results indicated that with this technique it is possible to clearly separate the wines aged by the three systems (chips, staves, and barrels) in the case of American oak. In the case of French oak, wines aged with chips were clearly differentiated for wines from a single grape variety and with similar oenological features.
The most recent paper on this topic [96] analyzed approximately 90 red wines issued from the same wine appellation in Italy, including commercial barrel-aged wines and wines aged using different types of commercial oak chips. Wines were analyzed in transmittance using NIR. In order to test if combined explanatory variables made it possible to discriminate treatments, an orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out. Several factors were considered, including the aging process, the type of oak used for aging (wood
It is worth noting that IR spectroscopy has been used in other studies on wine aging, although without direct comparison between wood alternatives and barrel aging. For instance, FT-IR and UV-visible (UV-Vis) spectroscopic techniques combined with multivariate analysis were used to obtain regression models to study the aging level of high-quality Sherry wines [106]. Moreover, [105] wines aged in barrels made from different wood species and in stainless steel tanks, were analyzed. A complete differentiation of the samples was achieved according to grape variety, the container type and the aging time based on two spectral regions of their FT-IR spectra. The overall significance of these studies is still provisional because of the restricted data sets and the inhomogeneity of spectral ranges analyzed in the different papers. However, the results show the potential of IR spectroscopy and chemometric analysis for discriminating wines issued from different aging processes. In this regard, identifying discriminating algorithms and creating robust databases is a necessary condition to obtain a method that can be used routinely in a laboratory for quickly acquiring specific information about the type of wood used for wine aging.
Finally, nuclear magnetic resonance (NMR) is a powerful tool for analysis, quality control and authentication of wines. The main advantage of non-targeted wine analysis by 1H NMR spectroscopy is the ability to collect, relatively simply and fastly, a huge amount of compositional information relating to a single sample [109]. Unlike other analytical techniques, however, it requires complex instrumentation and specialized personnel to be realized, but thanks to its versatility and reproducibility, this analytical technique seems to be very promising for the purposes described in this chapter.
In modern winemaking, oak products alternative to barrels are useful and flexible tools for wineries, enabling them to meet the needs of an increasingly wide and varied market. The compounds from oak wood impart a typical aromatic profile to wine and contribute to the increased polyphenolic patrimony of the final wine. Recently, the use of wood fragments has expanded, and new formats of alternative products have been added to those already known, significantly improving wine quality and dramatically increasing the opportunities of choice. Major advantages associated with the use of these products concern the reduction of both costs and production times. Furthermore, it enables the possibility of obtaining standardized wines whose compositional and sensory characteristics are very close to those defined in the phase of product design; in addition, the reduction of microbiological risks associated with the use of barrels is not negligible. Among the factors that most influence the sensory quality of the final wine, the dose of oak chips, the level of toasting and the moment of application must be considered. The different geographical and botanical origin of the chips seems to secondarily affect the result.
From a sensory point of view, it is not easy to distinguish products obtained by aging with chips from those obtained traditionally. Considering the consumer preference between oak chips and barrel wines, the variability among tasters is very high depending on the age and experience (e.g., young tasters and experienced tasters) and winemakers could take in consideration the specific preferences of different consumer groups. The distinction of the two different products is therefore mainly possible through laboratory investigation techniques: analytical methods allow expanding the compositional differences between the two products both for commercial purposes, but also for the control of fraudulent activities if necessary. Among the analytical techniques used, the spectroscopic ones are certainly those that, combined with multivariate statistics techniques, allow to obtain the best results in this field.
The possibility of refining wines with chips, staves or other alternative products, does not therefore oppose the use of barrels, but represents an additional option and a further opportunity for winemakers to obtain high-quality products. The two types of wines can today coexist in the wine global market, appreciated by different segments of consumers.
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Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"39599",doi:"10.5772/50046",title:"Encapsulation Technology to Protect Probiotic Bacteria",slug:"encapsulation-technology-to-protect-probiotic-bacteria",totalDownloads:12448,totalCrossrefCites:45,totalDimensionsCites:87,abstract:null,book:{id:"3145",slug:"probiotics",title:"Probiotics",fullTitle:"Probiotics"},signatures:"María Chávarri, Izaskun Marañón and María Carmen Villarán",authors:[{id:"150285",title:"Dr.",name:"María",middleName:null,surname:"Chávarri Hueda",slug:"maria-chavarri-hueda",fullName:"María Chávarri Hueda"},{id:"151613",title:"MSc.",name:"Izaskun",middleName:null,surname:"Marañon",slug:"izaskun-maranon",fullName:"Izaskun Marañon"},{id:"151621",title:"Dr.",name:"Mª Carmen",middleName:null,surname:"Villarán",slug:"ma-carmen-villaran",fullName:"Mª Carmen Villarán"}]},{id:"39607",doi:"10.5772/50121",title:"Recent Application of Probiotics in Food and Agricultural Science",slug:"recent-application-of-probiotics-in-food-and-agricultural-science",totalDownloads:10168,totalCrossrefCites:32,totalDimensionsCites:77,abstract:null,book:{id:"3145",slug:"probiotics",title:"Probiotics",fullTitle:"Probiotics"},signatures:"Danfeng Song, Salam Ibrahim and Saeed Hayek",authors:[{id:"107905",title:"Prof.",name:"Salam",middleName:null,surname:"Ibrahim",slug:"salam-ibrahim",fullName:"Salam Ibrahim"},{id:"150202",title:"Dr.",name:"Danfeng",middleName:null,surname:"Song",slug:"danfeng-song",fullName:"Danfeng Song"},{id:"151025",title:"MSc.",name:"Saeed",middleName:null,surname:"Hayek",slug:"saeed-hayek",fullName:"Saeed Hayek"}]},{id:"49246",doi:"10.5772/61300",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4720,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. 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These data are crucial to improve the performance, robustness and stability of biofilm-based wastewater treatment technologies.",book:{id:"5197",slug:"microbial-biofilms-importance-and-applications",title:"Microbial Biofilms",fullTitle:"Microbial Biofilms - Importance and Applications"},signatures:"Shama Sehar and Iffat Naz",authors:[{id:"180364",title:"Dr.",name:"Iffat",middleName:null,surname:"Naz",slug:"iffat-naz",fullName:"Iffat Naz"},{id:"183345",title:"Dr.",name:"Shama",middleName:null,surname:"Sehar",slug:"shama-sehar",fullName:"Shama Sehar"}]}],mostDownloadedChaptersLast30Days:[{id:"65613",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9260,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"62553",title:"Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance",slug:"antibiotic-use-in-poultry-production-and-its-effects-on-bacterial-resistance",totalDownloads:7315,totalCrossrefCites:42,totalDimensionsCites:89,abstract:"A surge in the development and spread of antibiotic resistance has become a major cause for concern. Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"65914",title:"Introductory Chapter: The Action Mechanisms of Antibiotics and Antibiotic Resistance",slug:"introductory-chapter-the-action-mechanisms-of-antibiotics-and-antibiotic-resistance",totalDownloads:4416,totalCrossrefCites:6,totalDimensionsCites:10,abstract:null,book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu, Nesrin Gareayaghi and Bekir S. Kocazeybek",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"},{id:"248288",title:"Prof.",name:"Bekir",middleName:null,surname:"Kocazeybek",slug:"bekir-kocazeybek",fullName:"Bekir Kocazeybek"},{id:"406463",title:"Dr.",name:"Nesrin",middleName:null,surname:"Gareayaghi",slug:"nesrin-gareayaghi",fullName:"Nesrin Gareayaghi"}]},{id:"50992",title:"Probiotics: A Comprehensive Review of Their Classification, Mode of Action and Role in Human Nutrition",slug:"probiotics-a-comprehensive-review-of-their-classification-mode-of-action-and-role-in-human-nutrition",totalDownloads:5418,totalCrossrefCites:16,totalDimensionsCites:28,abstract:"Probiotics are live microorganisms that live in gastrointestinal (GI) tract and are beneficial for their hosts and prevent certain diseases. In this chapter, after a complete introduction to probiotics, definition, mechanism of action, and their classification, currently used organisms will be discussed in detail. Moreover, different kinds of nutritional synthetic products of probiotics along with their safety and drug interaction will be noticed. This chapter mentions all clinical trial studies that have been done to evaluate probiotic efficacy with a focus on gastrointestinal diseases.",book:{id:"5193",slug:"probiotics-and-prebiotics-in-human-nutrition-and-health",title:"Probiotics and Prebiotics in Human Nutrition and Health",fullTitle:"Probiotics and Prebiotics in Human Nutrition and Health"},signatures:"Amirreza Khalighi, Reza Behdani and Shabnam Kouhestani",authors:[{id:"179560",title:"Dr.",name:"Amirreza",middleName:null,surname:"Khalighi",slug:"amirreza-khalighi",fullName:"Amirreza Khalighi"},{id:"185238",title:"Dr.",name:"Reza",middleName:null,surname:"Behdani",slug:"reza-behdani",fullName:"Reza Behdani"},{id:"185239",title:"Dr.",name:"Shabnam",middleName:null,surname:"Kouhestani",slug:"shabnam-kouhestani",fullName:"Shabnam Kouhestani"}]},{id:"72109",title:"Antibiotic Resistance in Biofilm",slug:"antibiotic-resistance-in-biofilm",totalDownloads:1473,totalCrossrefCites:11,totalDimensionsCites:20,abstract:"Biofilms can be found on several living and nonliving surfaces, which are formed by a group of microorganisms, complex assembly of proteins, polysaccharides, and DNAs in an extracellular polymeric matrix. By forming a biofilm, bacteria protect themselves from host defense, disinfectants, and antibiotics. Bacteria inside biofilm are much more resistant to antimicrobial agents than planktonic forms since bacteria that are unresisting to antimicrobial agents in any way can turn resistant after forming a biofilm. Low penetration of antibiotics into the biofilm, slow reproduction, and the existence of adaptive stress response constitute the multiphased defense of the bacterium. This antibiotic resistance, which is provided by biofilm, makes the treatments, which use effective antibiotic doses on the bacterium in planktonic shape, difficult. Biofilm formation potential of bacteria appears as an important virulence factor in ensuring the colonization on the living tissues or medical devices and makes the treatment difficult. The aim of this chapter is to overview the current knowledge of antimicrobial resistance mechanisms in biofilms.",book:{id:"8967",slug:"bacterial-biofilms",title:"Bacterial Biofilms",fullTitle:"Bacterial Biofilms"},signatures:"Sadık Dincer, Fatima Masume Uslu and Anil Delik",authors:[{id:"188141",title:"Prof.",name:"Sadik",middleName:null,surname:"Dincer",slug:"sadik-dincer",fullName:"Sadik Dincer"},{id:"315992",title:"MSc.",name:"Fatıma Masume",middleName:null,surname:"Uslu",slug:"fatima-masume-uslu",fullName:"Fatıma Masume Uslu"},{id:"315993",title:"MSc.",name:"Anıl",middleName:null,surname:"Delik",slug:"anil-delik",fullName:"Anıl Delik"}]}],onlineFirstChaptersFilter:{topicId:"148",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81704",title:"Quorum Sensing Inhibition Based Drugs to Conquer Antimicrobial Resistance",slug:"quorum-sensing-inhibition-based-drugs-to-conquer-antimicrobial-resistance",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104125",abstract:"Quorum sensing is the cell to cell communication mechanism in microorganism through signalling molecules. Regulation of virulence factor, sporulation, proteolytic enzymes production, biofilm formation, auto-inducers, cell population density are key physiological process mediated through quorum-sensing (QS) signalling. Elevation of innate immune system and antibiotic tolerance of pathogens is highly increased with perspective of quorum-sensing (QS) activity. Development of novel drugs is highly attractive scenario against cell-cell communication of microbes. Design of synthetic drugs and natural compounds against QS signal molecules is vital combat system to attenuate microbial pathogenicity. Quorum sensing inhibitors (QSIs), quorum quenchers (QQs), efflux pump inhibitors (EPIs) act against multi-drug resistance strains (MDR) and other pathogenic microbes through regulation of auto-inducers and signal molecule with perceptive to growth arrest both in-vitro and in-vivo. QQs, QSIs and EPIs compounds has been validated with various animal models for high selection pressure on therapeutics arsenal against microbe’s growth inhibition. Promising QSI are phytochemicals and secondary metabolites includes polyacetylenes, alkaloids, polyphenols, terpenoids, quinones.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Kothandapani Sundar, Ramachandira Prabu and Gopal Jayalakshmi"},{id:"82372",title:"Unlocking the Potential of Ghost Probiotics in Combating Antimicrobial Resistance",slug:"unlocking-the-potential-of-ghost-probiotics-in-combating-antimicrobial-resistance",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104126",abstract:"Antimicrobial resistance is a global concern that requires immediate attention. Major causes of development of antimicrobial resistance in microbial cells are overuse of antimicrobials along the food chain especially in livestock, in preventing infections as well as misuse of antimicrobials by patients. Probiotics could be a viable alternative to antibiotics in the fight against antimicrobial resistance. Probiotic strains can act as a complement to antimicrobial therapy, improving antimicrobial function and enhancing immunity. However, there are safety concerns regarding the extensive use of live microbial cells especially in immunocompromised individuals; these include microbial translocation, inhibition of other beneficial microorganisms and development of antimicrobial resistance, among other concerns. Inevitably, ghost probiotics have become the favored alternative as they eliminate the safety and shelf-life problems associated with use of probiotics. Ghost probiotics are non-viable microbial cells (intact or broken) or metabolic products from microorganisms, which when administered in adequate amounts have biologic activity in the host and confer health benefits. Ghost probiotics exert biological effects similar to probiotics. However, the major drawback of using ghost probiotics is that the mechanism of action of these is currently unknown, hence more research is required and regulatory instruments are needed to assure the safety of consumers.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Abigarl Ndudzo, Sakhile Ndlovu, Nesisa Nyathi and Angela Sibanda Makuvise"},{id:"82178",title:"Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role of One Health",slug:"managing-antimicrobial-resistance-beyond-the-hospital-antimicrobial-stewardship-the-role-of-one-heal",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.104170",abstract:"Infections caused by micro-organisms affect the health of people and animals, causing morbidity and mortality, with Asia and Africa as the epicenters. Some of the infectious diseases are emerging and re-emerging in nature. Examples include viral hepatitis, Lassa fever, Ebola, yellow fever, tuberculosis, covid-19, measles, and malaria, among others. Antimicrobials have been playing an important role in the treatment of infections by these microbes. However, there has been a development of resistance to these antimicrobials as a result of many drivers. This write-up used secondary data to explore the management of antimicrobial resistance (AMR) beyond the hospital antimicrobial resistance steward using the one health concept. The findings showed AMR to be a transboundary, multifaceted ecosystem problem affecting both the developed and developing countries. It is also one of the top ten global public health threats facing mankind. Globally, AMR will cost over US$100 trillion in output loss by 2050, about 700,000 deaths a year, and 4,150,000 deaths in Africa by 2050. About 2.4 million people could die in high-income countries between 2015 and 2050 without a sustained effort to contain AMR. The drivers of AMR are beyond the hospital and hospital AMR stewardship. Therefore, the need for one health concept to manage it.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Istifanus Anekoson Joshua, Mathew Bobai and Clement Sokfa Woje"},{id:"81918",title:"Machine Learning for Antimicrobial Resistance Research and Drug Development",slug:"machine-learning-for-antimicrobial-resistance-research-and-drug-development",totalDownloads:52,totalDimensionsCites:0,doi:"10.5772/intechopen.104841",abstract:"Machine learning is a subfield of artificial intelligence which combines sophisticated algorithms and data to develop predictive models with minimal human interference. This chapter focuses on research that trains machine learning models to study antimicrobial resistance and to discover antimicrobial drugs. An emphasis is placed on applying machine learning models to detect drug resistance among bacterial and fungal pathogens. The role of machine learning in antibacterial and antifungal drug discovery and design is explored. Finally, the challenges and prospects of applying machine learning to advance basic research on and treatment of antimicrobial resistance are discussed. Overall, machine learning promises to advance antimicrobial resistance research and to facilitate the development of antibacterial and antifungal drugs.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Shamanth A. Shankarnarayan, Joshua D. Guthrie and Daniel A. Charlebois"},{id:"81891",title:"Alternatives to Antibiotics in Semen Extenders Used in Artificial Insemination",slug:"alternatives-to-antibiotics-in-semen-extenders-used-in-artificial-insemination",totalDownloads:27,totalDimensionsCites:0,doi:"10.5772/intechopen.104226",abstract:"Antimicrobial resistance is a serious global threat requiring a widespread response. Both veterinarians and medical doctors should restrict antibiotic usage to therapeutic use only, after determining the sensitivity of the causal organism. However, the addition of antibiotics to semen extenders for animal artificial insemination represents a hidden, non-therapeutic use of antimicrobial substances. Artificial insemination for livestock breeding is a huge global enterprise with hundreds of million sperm doses prepared annually. However, reporting of antimicrobial resistance in semen is increasing. This review discusses the consequences of bacteria in semen samples, as well as the effect of antimicrobial substances in semen extenders on bacteria in the environment and even on personnel. Alternatives to antibiotics have been reported in the scientific literature and are reviewed here. The most promising of these, removal of the majority of bacteria by colloid centrifugation, is considered in detail, especially results from an artificial insemination study in pigs. In conclusion, colloid centrifugation is a practical method of physically removing bacteria from semen, which does not induce antibiotic resistance. Sperm quality in stored semen samples may be improved at the same time.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Jane M. Morrell, Pongpreecha Malaluang, Aleksandar Cojkic and Ingrid Hansson"},{id:"81699",title:"Efflux Pumps among Urinary E. coli and K. pneumoniae Local Isolates in Hilla City, Iraq",slug:"efflux-pumps-among-urinary-e-coli-and-k-pneumoniae-local-isolates-in-hilla-city-iraq",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.104408",abstract:"Urinary tract infections (UTI) are the most common bacterial infections affecting humans. Escherichia coli and Klebsiella pneumoniae were common enterobacteria engaged with community-acquired UTIs. Efflux pumps were vital resistance mechanisms for antibiotics, especially among enterobacteria. Overexpression of an efflux system, which results in a decrease in antibiotic accumulation, is an effective mechanism for drug resistance. The ATP-binding cassette (ABC) transporters, small multidrug resistance (SMR), and multidrug and toxic compound extrusion (MATE) families, the major facilitator superfamily (MFS), and the resistance-nodulation- cell division (RND) family are the five superfamilies of efflux systems linked to drug resistance. This chapter highlights the results of studying the prevalence of efflux pump genes among local isolates of E. coli and K. pneumoniae in Hilla City, Iraq. class RND AcrAB-TolC, AcrAD-TolC, and AcrFE-TolC genes detected by conventional PCR of E. coli and K. pneumoniae respectively. The result revealed approximately all studied efflux transporter were found in both E. coli and K. pneumoniae in different percentages. Biofilm formation were observed in 50(100%) of K. pneumoniae and 49(98%) of E. coli isolates were biofilm former and follow: 30(60%), 20(40%) were weak, 12(24%), 22(44%) were moderate and 7(14%) and 8(16%) were Strong biofilm former for E. coli and K. pneumoniae, respectively.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Hussein Al-Dahmoshi, Sahar A. Ali and Noor Al-Khafaji"}],onlineFirstChaptersTotal:13},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",isOpenForSubmission:!0,editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. He has published more than 400 works in his academic career and visited twenty-two universities worldwide as a visiting professor. Dr. Bobek is a member of the editorial boards of six international journals and a member of the Strategic Council of the Minister of Foreign Affairs of the Republic of Slovenia. He has a long history in academia, consulting, and entrepreneurship. His own consulting firm, Palemid, has managed twenty significant projects, such as Cooperation Program Interreg V-A (Slovenia-Austria) and Capacity Building for the Serbian Chamber of Enforcement Agents. He has also participated in many international projects in Italy, Germany, Great Britain, the United States, Spain, Turkey, France, Romania, Croatia, Montenegro, Malaysia, and China. Dr. Bobek is also a co-founder of the Academy of Regional Management in Slovenia.",institutionString:"Universities of Applied Sciences FH Joanneum, Austria",institution:{name:"Universities of Applied Sciences Joanneum",institutionURL:null,country:{name:"Austria"}}},editorTwo:{id:"293992",title:"Dr.",name:"Tatjana",middleName:null,surname:"Horvat",slug:"tatjana-horvat",fullName:"Tatjana Horvat",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hXb0hQAC/Profile_Picture_1642419002203",biography:"Tatjana Horvat works as a professor for accountant and auditing at the University of Primorska, Slovenia. She is a Certified State Internal Auditor (licensed by Ministry of Finance RS) and Certified Internal Auditor for Business Sector and Certified accountant (licensed by Slovenian Institute of Auditors). At the Ministry of Justice of Slovenia, she is a member of examination boards for court expert candidates and judicial appraisers in the following areas: economy/finance, valuation of companies, banking, and forensic investigation of economic operations/accounting. At the leading business newspaper Finance in Slovenia (Swedish ownership), she is the editor and head of the area for business, finance, tax-related articles, and educational programs.",institutionString:null,institution:{name:"University of Primorska",institutionURL:null,country:{name:"Slovenia"}}},editorThree:null},{id:"87",title:"Economics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/87.jpg",isOpenForSubmission:!0,editor:{id:"327730",title:"Prof.",name:"Jaime",middleName:null,surname:"Ortiz",slug:"jaime-ortiz",fullName:"Jaime Ortiz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002zaOKZQA2/Profile_Picture_1642145584421",biography:"Dr. Jaime Ortiz holds degrees from Chile, the Netherlands, and the United States. He has held tenured faculty, distinguished professorship, and executive leadership appointments in several universities around the world. Dr. Ortiz has previously worked for international organizations and non-government entities in economic and business matters, and he has university-wide globalization engagement in more than thirty-six countries. He has advised, among others, the United Nations Development Program, Inter-American Development Bank, Organization of American States, Pre-investment Organization of Latin America and the Caribbean, Technical Cooperation of the Suisse Government, and the World Bank. Dr. Ortiz is the author, co-author, or editor of books, book chapters, textbooks, research monographs and technical reports, and refereed journal articles. He is listed in Who’s Who in the World, Who’s Who in America, Who’s Who in Finance and Business, Who’s Who in Business Higher Education, Who’s Who in American Education, and Who’s Who Directory of Economists. Dr. Ortiz has been a Fulbright Scholar and an MSI Leadership Fellow with the W.K. Kellogg Foundation. 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He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. 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He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. 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