The richest food sources of flavonoid groups determined by liquid chromatography [8].
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"9423",leadTitle:null,fullTitle:"AI and Learning Systems - Industrial Applications and Future Directions",title:"AI and Learning Systems",subtitle:"Industrial Applications and Future Directions",reviewType:"peer-reviewed",abstract:"Over the last few years, interest in the industrial applications of AI and learning systems has surged. This book covers the recent developments and provides a broad perspective of the key challenges that characterize the field of Industry 4.0 with a focus on applications of AI. The target audience for this book includes engineers involved in automation system design, operational planning, and decision support. Computer science practitioners and industrial automation platform developers will also benefit from the timely and accurate information provided in this work. The book is organized into two main sections comprising 12 chapters overall:
\r\n\tThe purpose of the book is to provide information on new scientific findings in space exploration and their application to other fields. Space exploration provides a fundamental source of knowledge that will improve our understanding of nature and its influence on our views. Its achievements will be directed to phenomena that require a proper explanation involving the analysis of data in studies of the solar system together with views on the origin of the universe and its evolution. The book should also contain aspects involved in the physical description of new phenomena and determine the manner in which they modify our present views and the techniques that we employ. Such contributions should also be accompanied by studies of their effects on human activity including the development of devices that will improve global communication. The importance of the book will be properly assessed by the value of its contributions.
\r\n\t
Polyphenols are the most common phytochemicals in human diet and comprise a variety of compounds with a great diversity of structures, ranging from simple molecules to polymers with high molecular weight. Polyphenols are plant secondary metabolites present in all plant tissues, and their primary role is to protect plants from insects, ultraviolet radiation, and microbial infections and to attract pollinators [1]. According to the chemical structures of aglycones, polyphenols are classified as flavonoids, phenolic acids, lignans, and stilbenes [2]. Fruits, vegetables, whole grains, chocolate, and drinks like tea and wine are good sources of polyphenols, but due to diverse chemical structures, it is difficult to estimate the total polyphenol content in foods. Beneficial health effects of these phytochemicals are directly linked to regular daily intake and bioavailability. The aim of this review is to present current knowledge regarding evidence on chronic disease prevention, factors affecting polyphenol bioavailability and bioaccessibility, and new trends in the production of polyphenol-enriched functional foods.
Dietary polyphenols comprise a variety of compounds among which flavonoids and several classes of non-flavonoids are usually distinguished. In nature, polyphenols are bound to sugars in the form of glycosides. However, classification of polyphenols in this review will be presented according to the chemical structures of aglycones. These compounds contain at least one aromatic ring and are classified into different groups according to the number of aromatic rings and the structural elements that bind these rings together. Therefore, polyphenols are classified as flavonoids, phenolic acids, lignans, and stilbenes [2].
Chemical structures of flavonoids [
Flavonoid subgroup | Food source | Content (mg/100 g) |
---|---|---|
Flavonols | Capers | 654.71 |
Saffron | 509.99 | |
Mexican oregano (dried) | 272.07 | |
Red onion (raw) | 128.51 | |
Spinach (raw) | 119.27 | |
Flavones | Celery seed | 2094.00 |
Peppermint (dried) | 1486.29 | |
Common verbena (fresh) | 790.00 | |
Mexican oregano (dried) | 733.77 | |
Celery leaves (fresh) | 133.38 | |
Isoflavones | Soy (flour) | 466.99 |
Soy paste (cheonggukang) | 264.40 | |
Soybean (roasted) | 246.95 | |
Soy (tempeh) | 147.72 | |
Soy paste (nato) | 103.90 | |
Flavanones | Peppermint (dried) | 8739.98 |
Mexican oregano (dried) | 1049.67 | |
Grapefruit/pummelo hybrid (pure juice) | 67.08 | |
Orange (juice from concentrate) | 61.29 | |
Rosemary (fresh) | 55.05 | |
Anthocyanidins | Black elderberry | 1316.65 |
Black chokeberry | 878.12 | |
Black currant (raw) | 592.23 | |
Lowbush blueberry (raw) | 187.23 | |
Blackberry (raw) | 172.59 | |
Flavanols | Cocoa (powder) | 511.62 |
Chocolate (dark) | 212.36 | |
Broad bean pod (raw) | 154.45 | |
Black tea (infusion) | 73.30 | |
Green tea (infusion) | 71.17 |
The richest food sources of flavonoid groups determined by liquid chromatography [8].
The most common
The best sources of
The most important
Chemical structure of phenolic acids [
The most important derivatives of cinnamic acids are coumaric, caffeic, ferulic, and sinapic acids. In food, they are often in the bound form and can only be released upon acid or alkaline hydrolysis or by enzymes. Caffeic acid is the most abundant phenolic acid and represents about 87% of the total hydroxycinnamic acid content of most fruits [2]. Caffeic and quinic acid together form chlorogenic acid, which makes up about 10% of green Robusta coffee beans. Regular consumption of coffee may provide more than 1 g of chlorogenic acid, which means that for many people it is the main source of dietary polyphenol [1].
Chemical structure of lignans [
Chemical structure of stilbenes [
Polyphenols are the most common phytochemicals in human diet and are in the focus of scientific research due to their biological properties, bioavailability, and bioaccessibility, as well as their effects on the prevention of chronic diseases. Epidemiological studies confirm that moderate and prolonged intake of foods rich in polyphenols could prevent the formation of cancer and chronic diseases such as cardiovascular disease, neurodegenerative disease, type 2 diabetes, and obesity, which are the most common in Western populations [1].
A large primary prevention trial tested the long-term effects of the Mediterranean diet, containing polyphenol-rich foods, on the incidence of cardiovascular disease in participants with high risk but free of cardiovascular disease at baseline (the PREDIMED study). Data on their dietary habits were collected with a validated food frequency questionnaire, and the polyphenol content in foods was obtained from the Phenol-Explorer database. Results showed a significant reduction of cardiovascular events and cardiovascular mortality with a higher intake of total polyphenols, especially flavanols, lignans, and hydroxybenzoic acids [11]. The aim of this study was also to investigate the effect of polyphenol intake on all-cause mortality. Among high-risk subjects, those with higher polyphenol intake showed a 37% lower mortality risk, compared with those with lower intake. Subgroups of polyphenols with the strongest inverse association were stilbenes and lignans, while flavonoids and phenolic acids had no significant effect on mortality reduction [12]. However, the European Prospective Investigation into Cancer and Nutrition (EPIC) reported that higher flavonoid intake in the diet was associated with a 29% reduction in all-cause mortality, in particular for the subclasses of flavanones and flavonols, which decreased the incidence of cardiovascular disease by 40 and 41%, respectively [13]. Although a beneficial effect has been proven, more controlled trials are needed to definitively clarify the benefits of different polyphenol subgroups and to define minimum levels of dietary intake. Beneficial effects of polyphenols on cardiovascular disease have been attributed to their antioxidant activities, but recent evidence suggests that vasodilatory, anti-inflammatory, and anti-atherogenic properties may also contribute to cardiovascular risk reduction, indicate their ability to improve lipid profile, and modulate apoptotic processes in the vascular endothelium [14].
Growing evidence also indicates that polyphenols may prevent neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease by decreasing inflammatory stress signaling, leading to the expression of genes that encode antioxidant enzymes and cytoprotective proteins [15]. A study conducted by Schmidt et al. [16] showed that green tea extracts can increase the number of connections between neurons of frontal and parietal brain regions which positively correlated with the improvement in the task performance. A double-blind study included 12 healthy volunteers who received either a milk solution with 27.5 g of green tea extract or a milk solution without the extract. The effect of green tea extract on working memory was visualized with functional magnetic resonance imaging (MRI) while performing memory test. Another intervention study confirmed the beneficial effect of blueberries. During 12 weeks of blueberry juice consumption, cognitive function (paired associate learning and word list recall) was significantly improved in older patients with early symptoms of dementia. In addition, symptoms of depression and blood glucose levels were reduced [17].
Many studies investigated the impact of polyphenols on carbohydrate metabolism and possible prevention of diabetes type 2. Polyphenols have the potential to inhibit key enzymes that are responsible for the digestion of dietary carbohydrates (α-amylase and α-glucosidase) and thus modify the postprandial glycemic response [18]. In vitro studies have shown that polyphenol-rich extracts from berries are effective in the inhibition of α-amylase and α-glucosidase at low levels. Tannin-like components (ellagitannins and proanthocyanidins) from raspberry and rowanberry were the most effective for amylase inhibition. A rowanberry fraction rich in proanthocyanidins was as equally strong an inhibitor as the whole rowanberry extract for α-amylase inhibition but was considerably less effective for α-glucosidase inhibition which suggests that tannins are poor inhibitors of α-glucosidase. Among the tested berry extracts, black currants rich in anthocyanins and flavonols had the strongest inhibitory effect on α-glucosidase [19]. The aim of an interesting study conducted by Yang and Kong [20, 21] was to investigate the effect of green tea polyphenols and green, black, and oolong tea extracts on α-amylase and α-glucosidase activity. All tested samples showed a strong inhibitory effect on α-glucosidase, and their inhibitory potency is mainly attributed to tea polyphenols. In contrast, all three types of tea extract significantly enhanced α-amylase activity, whereas green tea showed the highest activation effect. Green tea polyphenols significantly increased α-amylase activity in low concentrations. A high concentration, however, resulted in a mild inhibitory effect, suggesting that other constituents in the tea counteract the inhibitory effect of polyphenols. A large prospective EPIC-InterAct study examined the association between dietary flavonoid and lignan intake and the risk of developing diabetes type 2 in eight European countries. High intake of flavonoids was associated with a significant risk reduction, while the intake of lignans had no effect. Among flavonoid subclasses, flavonols and flavanols were associated with a significantly reduced risk of diabetes [22]. A comprehensive review by Kim et al. [18] summarizes epidemiological and clinical studies that investigated the relationship between food rich in polyphenols and risk of diabetes type 2. Despite promising data from in vitro and animal studies, the number of intervention surveys conducted on human beings is small. Most studies showed that polyphenols were associated with a lower risk of diabetes type 2, but this association was not entirely consistent. Potential mechanisms of the action of polyphenols in preventing diabetes type 2 include the stimulation of insulin secretion and protection of pancreatic β-cells against glucose toxicity, in addition to the inhibition of salivary and pancreatic α-amylase and α-glucosidase.
Obesity is considered one of the most serious health problems that have assumed the character of a global epidemic. According to the data published by Eurostat in 2014, 51.6% of adults in the European Union are overweight (35.7% pre-obese and 15.9% obese). The in vitro and some in vivo studies suggested that consumption of particular polyphenols (such as catechin in green tea, anthocyanins in blueberries, resveratrol in wine, and curcumin in turmeric) may facilitate weight loss and prevent weight gain due to changes in lipid and energy metabolism [23]. A survey conducted by Basu et al. [24] showed that using a freeze-dried blueberry beverage in obese people with metabolic syndrome for 8 weeks decreased blood pressure and the concentrations of oxidized LDL cholesterol and products of lipid peroxidation. Some researchers suggested that polyphenols may inhibit lipase activity and consequently reduce lipid absorption [25, 26]. Uchiyama et al. [27] have shown that black tea polyphenols in rats with diet-induced obesity can inhibit intestinal lipase activity and suppress the increase of triglyceride levels.
The cause of the aforementioned chronic disease can be associated with oxidative stress resulting from reactive oxygen and nitrogen species. Many in vitro studies have demonstrated that polyphenols can decrease inflammatory markers, reduce oxidative stress, and improve cancer biomarkers, but intervention studies have not always confirmed these positive effects. The reasons which could explain these differences include different doses of administered compounds, polyphenol instability in food and in the gastrointestinal system, a synergistic effect with other antioxidants from the whole food, differences in bioavailability as a result of release from the food matrix, and the presence of food components in the matrix which may enhance or reduce polyphenol bioavailability [28].
The beneficial effects of polyphenols on human health depend considerably on dietary intake. Due to the great diversity of their chemical structures, it is difficult to estimate the total polyphenol content in foods. Hence, a comprehensive database was developed to help estimate the polyphenol content in certain foods and has been available online since 2009 [8]. Data summarized there were derived from more than 1300 scientific publications. According to this database, Pérez-Jiménez et al. [29] established a list of the 100 richest dietary sources of polyphenols per 100 g of food and in a food serving, using common serving sizes. Data on the total content of polyphenols were calculated based on the sum of all individual polyphenol contents determined by chromatography. In addition, the results were compared with data obtained by the Folin-Ciocalteu method, one of the most commonly used method for estimating total phenolic content. The results showed that the richest sources per 100 g of foods are various herbs and cocoa products (as shown in Table 1), while at the top of the list, expressed per serving size, are various darkly colored berries such as black elderberry, chokeberry, black currant, and blueberry. Comparison of the data obtained by different methods showed that the values obtained by the Folin-Ciocalteu method systematically exceed the total amount of polyphenols because this method is not specific and interference with other antioxidants present in the food is possible.
With the aim of estimating polyphenol intake, a large European cohort study was recently conducted in ten countries on more than 36,000 subjects. The results showed that the largest intake of phenolic compounds is in Denmark (1706 mg/day), while the lowest is in Greece (664 mg/day). Similar findings were observed after comparison of intake according to regions; the total polyphenol intake in the non-Mediterranean countries was higher compared with the Mediterranean countries. The most significant sources of phenolic compounds are coffee, tea, and fruit, with phenolic acids contributing to the total intake with more than 50% [30]. This was the first study that applied retention factors from the Phenol-Explorer database to assess the effects of cooking and processing on polyphenol contents in foods. Although the usual cooking of common plant foods causes substantial losses of polyphenols, in this study it did not have a high impact on the estimated total polyphenol intake because vegetables and legumes were not major contributors to polyphenol intake [31].
Research on the dietary intake of phenolic compounds has been conducted also in certain European countries, and the results show that the average intake in France is 1193 mg/day [32], in Poland 1756.5 mg/day [33], and in Spain 820 mg/day [34]. The main dietary sources of the total polyphenols in Spain and France are fruits and nonalcoholic beverages (principally coffee and tea). In Spain, fruits accounted for 44% of the total polyphenol intake and nonalcoholic beverages for 23%, whereas in France fruit accounted for only 17% and nonalcoholic beverages for 55% of the total polyphenol intake. Considering individual foods, the main source of total dietary polyphenols is coffee with 18 and 44% of contribution in Spain and France, respectively. In Spain, in contrast to other countries, olives and olive oils are important sources of polyphenols, accounting for 11% of the total polyphenol intake. Nonalcoholic beverages were the main food contributors to polyphenol intake in Poland and accounted for fully 67% of the total polyphenol intake due to high consumption of coffee and tea. The third main contributor to total polyphenol intake is chocolate, whereas fruits accounted for a lower percentage of intake.
The beneficial effects of phenolic compounds on health depend not only on food sources but also on their stability, which can vary depending on the method of raw material processing, the matrix in which they are incorporated, and endogenous factors such as microbiota and digestive enzymes. The fraction of the phenolic compounds that can be released from the food matrix by digestive enzymes or intestinal bacterial flora in the colon is bioaccessible and, therefore, potentially bioavailable for absorption [28]. The FDA has defined bioavailability as the rate and extent to which the active substances or therapeutic moieties contained in a drug are absorbed and become available at the site of the action [35].
Understanding the effects of food processing on polyphenol content and bioavailability is important since most of the food consumed on a daily basis is in a processed form. Conventional methods of thermal processing, such as pasteurization that is still most commonly used, provide microbiological stability and extend shelf life but also cause some undesirable changes such as degradation of polyphenols and other bioactive compounds. The possibility of ensuring food safety and at the same time preserving biologically active compounds has resulted in increased interest in the minimal processing of foods using nonthermal methods, such as high-pressure processing and ultrasound. Studies have demonstrated that in comparison with high-pressure processing, pasteurization causes more degradation of polyphenol, anthocyanins, vitamin C, and the color of strawberry puree [36]. Treatment with high-intensity ultrasound, due to the cavitation effect, can break down cell walls and facilitate the extraction of bioactive compounds, thus increasing their bioavailability. Additionally, increased antioxidant capacity and monomeric anthocyanin content in red raspberry puree treated with high-intensity ultrasound were achieved by Golmohamadi et al. [37].
Food matrix composition and other food components significantly influence bioaccessibility, uptake, and further metabolism of polyphenols. Before becoming bioavailable, polyphenols must be released from the food matrix and hydrolyzed by intestinal enzymes or microflora to aglycones. In vitro gastrointestinal digestion models are a useful tool for assessing the impact of the food matrix and other endogenous factors on the stability and biological activity of phenolic compounds and can be well correlated with results from human studies and animal models [38]. Simulation of the physiological parameters, such as variation in the enzymes, acid and bile salt excretion, availability of the substrate, and the transit time of food through the stomach and duodenum, is challenging in all in vitro digestion models. Gastric digestion is simulated by pepsin-HCl at pH 2 and small intestinal digestion with pancreatin-bile mixture at pH 7, while the absorption step can be simulated with polarized human colon carcinoma cell line (Caco-2 cells) [39]. Commercial digestive enzymes, collected or extracted from omnivorous animals, are most commonly used, but their role in the simulation of the human digestion process is still questionable. On the other hand, human digestive juices contain a complex mixture of different enzymes, enzyme inhibitors, and bile salts, which together contribute to the digestion process of food; therefore, the use of human digestive juices may represent a great advantage over commercial digestive enzymes [40]. Phenolic acids and flavonoids with small molecular weight such as gallic acid, catechins, and quercetin glucosides are easily absorbed through the tract, whereas large polyphenols such as proanthocyanidins are poorly absorbed [41]. In most of conducted studies, gastric digestion did not have a significant effect on polyphenol stability. In fact, the majority of polyphenols appear to be released in the stomach. Bouayed et al. [38] observed that approximately 65% of apple total phenolics and flavonoids were released in the stomach and only an additional 10% in the small intestine. Results of the study conducted by Correa-Betanzo et al. [42] showed a high stability of total polyphenols and anthocyanins (7 and 1% of reduction, respectively) during simulated gastric digestion, while intestinal digestion caused a significant decrease of 51 and 83%, respectively, in comparison with the non-digested wild blueberry samples. Similar results were obtained by Bermúdez-Soto et al. [43] who reported a significant reduction of anthocyanins (43%) and flavonols (26%) after intestinal digestion of chokeberry. Mild alkaline intestinal environment was shown to influence all phenolic compounds, especially anthocyanins, and it is generally accepted that their bioavailability is low (<1%). An interesting study was conducted by Czank et al. [44] who proved that bioavailability of anthocyanins has been underestimated. The participants consumed an isotopically labeled anthocyanin tracer (cyanidin-3-glucoside), and the concentration was determined in blood, urine, breath, and feces samples. Results showed a high combined recovery from urine and breathe, which was approximately 12%. To date, a little research has been conducted in investigating polyphenol stability by using human gastrointestinal enzymes. Zorić et al. [45] conducted a study on the stability of rosmarinic acid in an aqueous extract of thyme, lemon balm, and winter savory using human digestive juices of the stomach and small intestine. The results showed lower gastrointestinal stability of rosmarinic acid in comparison with similar studies with commercial digestive enzymes.
In the food matrix, polyphenols are usually mixed with different macromolecules such as proteins, lipids, and carbohydrates. Large polyphenols and those with a high number of hydroxyl groups have a high affinity for proteins, which can result in a complex formation that reduces polyphenol absorption [28]. Food rich in polyphenols, such as coffee or tea, is usually consumed with milk. Studies have shown that interactions between polyphenols and milk proteins, especially casein, can decrease the antioxidant activity of coffee and tea [46]. The effect of milk was confirmed in an intervention study by Serafini et al. [47] whose aim was to determine the total antioxidant capacity and (−)epicatechin content in blood plasma after consumption of plain dark chocolate, dark chocolate with full-fat milk, and milk chocolate. Results have shown that the addition of milk, either during ingestion or in the manufacturing process, caused a significant reduction in total antioxidant activity and absorption of (−)epicatechin in the bloodstream. The explanation was in the formation of a complex between chocolate flavonoids and milk proteins. However, not all studies showed the negative impact of milk addition to food on polyphenol absorption. Keogh et al. [48] monitored the concentration of catechin and epicatechin in the blood after consumption of chocolate polyphenols with and without milk proteins. Results showed that milk protein did not influence the average plasma polyphenol concentration after ingestion. Contradictory results of these and many other studies were explained by the influence of polyphenol concentration. Milk could inhibit absorption in the case of lower polyphenol concentration, while it could have only minimal impact if the concentration is high [35]. In addition to food proteins, polyphenols can also bind to digestive enzymes and act as effective inhibitors as previously described in Chapter 3.
Only a few studies have investigated the interactions between polyphenols and dietary lipids. Since most polyphenols are water soluble, dietary lipids are considered to have a limited influence. Some studies, however, have observed a positive relationship. Ortega et al. [49] found that higher fat content has a positive effect on the stability of cocoa polyphenols in an in vitro digestion model.
Interactions between polyphenols and dietary fibers are important since these interactions have a significant role in the human body. Most non-extractable polyphenols with higher molecular weight (such as tannins and proanthocyanidins) are usually attached with covalent bounds to dietary fibers [28]. The bioavailability of polyphenols depends on the release of polyphenols from such a complex, which, in turn, depends on the polyphenols’ structure, the complexity of the polyphenol-carbohydrate structure, and the possibility of enzymes to reach the carbohydrates [35]. According to Ortega et al. [50], soluble dietary fibers, in the in vitro digestion model, enhanced the stability of phenolic compounds during duodenal digestion. Since dietary fibers act as an entrapping matrix and restrict the diffusion of the enzymes to their substrates in the stomach and small intestine, many polyphenols reach the large intestine [51]. Regardless of their bioavailability, polyphenols, as strong antioxidants, may contribute to a healthy antioxidant environment, thus protecting the colonic lumen from oxidative stress, and, furthermore, polyphenols and carbohydrates that have reached the large intestine can have a beneficial effect on colon microflora growth.
Today’s consumers’ expectations of food, besides appropriate taste, appearance, and price, are more focused on positive health effects. Since consumers’ awareness of health benefits associated with the consumption of food rich in polyphenols and preferences of herbal over synthetic products are increasing, meeting the consumers’ expectations is a key to success.
The global polyphenol market was valued USD 757 million in 2015, and it is estimated to exceed USD 1 billion by 2022 [52]. The most successful applications of plant extracts containing polyphenols are fortification of beverages, while the most popular plant extracts used in beverages and other types of functional food are grape seed, green tea, and apple extract. The market for functional food and the number of studies focused on functional food with a positive effect on health beyond basic nutrition are constantly growing. The bioavailability of functional food components and the levels required in humans are critical factors necessary to optimize health benefits [53]. Polyphenols are the most numerous and widely distributed group of functional molecules. Studies have shown that products enriched with polyphenols could be useful for the dietary management of diabetes and cardiovascular disease prevention. Blueberry polyphenol-enriched defatted soybean flour was incorporated into a very high-fat diet of obese and hyperglycemic mice for 13 weeks. Compared with the control group (very high-fat diet containing defatted soybean flour), the diet supplemented with blueberry polyphenols reduced weight gain, improved glucose tolerance, and lowered fasting blood glucose levels and serum cholesterol [54]. The aim of an intervention study conducted by Sarriá et al. [55] was to evaluate the effect of two cocoa functional products (one rich in dietary fibers and the other rich in polyphenols) on the markers of cardiovascular health. The most significant finding observed after consumption of both products was an increase in HDL cholesterol which was attributed to flavanols, the most common flavonoids in cocoa, while the fiber-rich product was associated with the hypoglycemic and anti-inflammatory effect. As recently reviewed by Tomé-Carneiro and Visioli [56], polyphenol-based nutraceuticals and functional food might be used as adjunct therapy for cardiovascular disease.
Since it is generally accepted that the bioavailability of polyphenols is rather low, recent scientific studies are focused on the enhancement of polyphenol bioaccessibility and the bioavailability rate in the body using encapsulation techniques such as spray-drying, freeze-drying, emulsions, and liposomes. Encapsulated polyphenols are more stable and are protected from light, oxygen, temperature, and moisture. Spray-drying is the most commonly applied encapsulation method in the food industry, transforming liquids into stable and easily applied powders, and can help in the controlled release of phenolic functional ingredients in the human body for more efficient nutraceutical usage [57]. Idham et al. [58] studied the degradation kinetics and color stability of spray-dried encapsulated anthocyanins with four different encapsulation agents (maltodextrin, gum Arabic, a combination of maltodextrin and gum Arabic, and soluble starch). Results have shown that the combination of maltodextrin and gum Arabic resulted in the highest encapsulation efficiencies as well as the longest shelf life and the smallest change in pigment color.
Emulsions are considered one of the most promising techniques for the protection and delivery of polyphenols, due to high-efficiency encapsulation, maintenance of chemical stability, and controlled release [59]. An emulsion is a mixture of two immiscible liquids, usually oil and water, with one of the liquids (the dispersed phase) being dispersed as small droplets in the other liquid (the continuous phase). Ru et al. [60] have shown that epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, encapsulated in oil-in-water (O/W) emulsions demonstrated an improved anticancer effect, compared with free EGCG, on human hepatocellular carcinoma cell lines. The unpleasant bitter taste of flavanol monomers (catechin and epicatechin) could be successfully masked by using encapsulation, thus increasing flavanol delivery in the gut [61].
Polyphenols comprise a large group of phytochemicals with very diverse chemical structures and are considered as being the most common antioxidants in the diet. Since many foods and beverages contain a diversity of polyphenols, it is difficult to determine which specific compounds are directly responsible for beneficial health effects in vivo. The health effects of polyphenols depend on both dietary intake and bioavailability, which can vary greatly. The strongest evidence for the beneficial effects of polyphenols with regard to chronic disease, cardiovascular diseases in particular, exists for flavanol-rich foods. Most dietary polyphenols have relatively short half-lives once ingested, due to rapid metabolism, so it is important that their consumption is maintained throughout the life span. More detailed knowledge on the relationship between the food matrix, processing, and bioavailability of polyphenols should lead to a better understanding of their role in human health and to the development of novel functional foods.
Misuse and abuse of antimicrobials are key contributors to the introduction of selective pressures in our natural environments, resulting in the rapid increase of antimicrobial resistant microbial strains. Random antimicrobial use has impelled microorganisms to adapt and survive by acquiring antimicrobial resistance genes that lead to antimicrobial resistant strains [1]. Antimicrobials are drugs or medicines, including antibacterials, antivirals, antifungals and antiparasitics, used to prevent and treat infections in humans, plants and animals [2]. Antimicrobial resistance occurs when a microbial strain is no longer susceptible to antimicrobials that would normally inhibit their growth and allows them to withstand the drugs [3]. Chromosomal or plasmid DNA encoding antimicrobial resistance is implicated in the rapid spread of multiple resistance through horizontal gene transfer [4], as shown in Figure 1.
Mechanisms of horizontal gene transfer in bacteria. Acquired antimicrobial resistance genes can pass between related and unrelated species by transformation, transduction and conjugation.
Mobile genetic elements including plasmids and transposons are instrumental in horizontal gene transfer [5]. Chromosomal resistance is caused by mutations in the developing spontaneous bacterial chromosome [6] while extra chromosomal resistance depends on the extra chromosomal genetic material that can be transferred in ways such as plasmids, transposons and integro [7]. Different types of resistance occur including natural resistance, acquired resistance, cross resistance and multi drug resistance [8, 9].
The major problem with antimicrobial resistance is the selection and stabilization of mechanisms directed by foreign genes taken up by susceptible and resistant strains [2]. Microorganisms can evade the effects of the antimicrobial agents throughdecreased influx (limiting uptake of a drug), alterationof drug target site, drug inactivation using enzymes and active drug efflux (efflux pump) [10, 11] as detailed in Figure 2.
Mechanisms of antibiotic resistance.
As a result of antimicrobial resistance, antibiotics and other antimicrobial medicines have become ineffective and infections are becoming increasingly difficult or impossible to treat increasing the risk of disease spread, severe illness and death. Alternative strategies are being employed in order to combat antimicrobial resistance. Such strategies include the use of probiotics.
Probiotics are live microorganisms, which when administered in correct proportions confer a health benefit on a host [12]. These microbes are a combination of bacteria, fungi, viruses and protozoa [13], and the commonly used probiotics are Lactobacillus and Bifidobacterium [14]. Beneficial probiotics are found in several locations on the body such as the gut, mouth, urinary tract, skin, lungs [8, 15]. Probiotic microorganisms can be isolated from plants, food products, environment, human and animal sources. Probiotics can be administered as supplements in a variety of forms, including in foods, drinks, capsules or pills, powders and liquids [16].
Microorganisms must possess a number of characteristics in order to be classified as probiotics, that is the microbes should be easily isolated from humans, have the ability to live in the gut after consumption, have a proven benefit and must be safe to consume [17, 18]. Some of the characteristics are shown in Figure 3.
Characteristics of probiotics.
Probiotics exert their biological effect using different mechanisms of action as shown in Figure 4, these include; inhibition of the growth of pathogenic bacteria (competitive exclusion), reduction of bacterial and/or toxin translocation, modulation of the intestinal immune system, production of specific substance such as bacteriocins, modifications of the structure and function of intestinal epithelium, competitive adhesion to epithelial receptors, vitamin absorption and provision of other nutrients [19, 20].
Mechanisms of action of probiotics.
Probiotics have a number of health benefits, including lowering the risk of some infectious diseases and reducing the need for antimicrobials to treat secondary infections. For example, the use of probiotics with antimicrobials reduces the incidence, duration and severity of antimicrobial-associated diarrhea, thereby reducing the evolution of resistance [21, 22, 23] and unlike antimicrobials which kill untargeted microbials, probiotics help to keep the gut microbiota in check. Some of the health benefits are shown in Table 1 below.
Probiotic health effects | |
---|---|
Metabolic effects | Microbiota & Immunomodulation effects |
|
|
Probiotics beneficial health effects.
Probiotics aren’t perfect, there are many safety challenges associated with the use of probiotics such as ability to acquire antimicrobial resistance and virulence genes [24], chances of microbial translocation from gut to the blood stream [25], high risk of allergic reactions [26] and that biological effects of probiotics are strain specific, therefore proper strain identification is required [27] for a specific condition. As a result, ghost probiotics have become the preferred alternative to probiotics in order to solve the majority of these safety issues [14].
Health benefits observed for physiologically active probiotics are not associated with their viability only [28]. Probiotic products containing dead cells can produce effective biological responses. This proves that probiotics merely have an expiry date and can be used beyond that. This phenomenon is known as the probiotic paradox, that is, both live and dead cells produce the same biological response [29]. Ghost probiotics (inactivated probiotics, non-viable probiotics, paraprobiotics) are inactive microbial cells or cell fractions that, when administered in adequate amounts, confer a health benefit to the consumer, [14, 30, 31]. They consist of molecules present on the cell surfaces such as peptidoglycan, teichoic acid, cell wall polysaccharides and cell surface-associated proteins [32]. These trigger the human immune system, stimulating a positive immune response and anti-inflammatory effects in animals and humans [33].
The methods used in producing ghost probiotics are similar to the techniques used for bacterial inactivation such as thermal processing, irradiation, UV rays, high pressure and ultrasound [14, 34] as shown in Table 2 below. Thermal treatment is the most common technique for the production of ghost probiotics in laboratories [14]. The cell membranes are damaged, leading to leakage of nutrients and ions, ribosome aggregation and DNA breakage. Ohmic heating has been proposed for ghost probiotics production. It involves an electric current passing through the sample, leading to fast and uniform heating [35]. Therefore, bacterial inactivation can be caused by thermal and non-thermal damage (electroporation). Inactivation methods have an impact on the beneficial effects. This means that ghost probiotics obtained with different technologies could exhibit different functional features [36].
Methods of cell inactivation | Activities that lead to cell inactivation |
---|---|
Thermal/ heat treatment |
|
High pressure treatment |
|
Ultra Violet (UV) Irradiation |
|
Ionizing radiations |
|
High intensity ultrasound |
|
Methods used in the production of ghost probiotics.
They are quite safe, they are well-tolerated and associated with reduced risk for adverse effects in vulnerable individuals [37]. They have no risk for transferring antibiotic-resistant genes to pathogenic or commensal bacteria [38]. Their effectivity is independent of the cell viability, which ensures longer stability and improved shelf-life [39]. They present an easy industrial large-scale production [36]. They provide a wide range of health-promoting effects, some of which can be reinforced in comparison with the effect of intact viable microbial cells [40]. Another very interesting feature of ghost probiotics, is that, due to their nature, it appears feasible that they could be used with concurrent administration with antibiotic and antifungal agents.
Ghost probiotics are categorized into peptidoglycan, teichoic acid, cell wall polysaccharides, cell surface-associated proteins and proteinaceous filaments. These are the ones that mediate beneficial effects to the host [41]. Some bacterial cell walls such as
Teichoic acids (TAs) are the second main constituent of the cell wall of the microbes. They possess immunomodulatory characteristics and exert anti-inflammatory effects on the intestinal epithelial cells of humans [43]. Cell-wall polysaccharides are common in Gram-positive bacteria surfaces for example exopolysaccharides (EPS). These have the ability to facilitate the interaction of the bacteria with pathogens, have immunoregulatory effects and act as a protective layer [43]. Cell surface proteins are one of the most important components of the outermost cell envelope structure. S-layer proteins, pili proteins, moonlight proteins are part of the surface proteins. These play a role in the host biological processes [44].
To counteract the phenomenon of antimicrobial resistance, there is a need to reduce the frequency in which they are administered. Ghost probiotics are used as a possible solution in fighting against antimicrobial resistance [45]. Due to the risks and concerns of administering probiotics to livestock, scientists are now opting to use ghost probiotics.
Cows tend to suffer from inflammation of the udder (mastitis). The main pathogens that stimulate the infection are
Increased animal production keeps animals crowded, facilitating the transmission of various diseases. The use of ghost probiotics on farms can naturally bring about a balance of gut microbes, reduce the growth of pathogens and reduce the use of antibiotics for disease prevention [49]. Thus, reducing the occurrence of resistance effects among pathogenic bacteria as the major spread of antimicrobial resistance is through food chains [50]. In a study carried out using
A variety of ghost probiotics from the
There is an innate immune response of macrophages to non-viable
The capability of ghost probiotics to safeguard the host’s health against serious infections induced by pathogens is fulfilled through various mechanisms such as inhibition of pathogenic adhesion, invasion, biofilm formation, and improvement of immune responses in thegut environment. Additionally, some ghost probiotics derived from
To address the safety concerns surrounding probiotics, the attention has switched to the use of non-viable microbial cells, commonly known as ghost probiotics. Ghost probiotic and probiotic cells exhibit similar immunological responses by means of using the same or different mechanisms of action [14, 31, 32]. This has been demonstrated by an experiment done on the human epithelial colorectal adenocarcinoma Caco-2 cell line, both viable and UV-inactivated
Furthermore, various inactivation methods for making ghost probiotics, such as high-pressure treatment and high-intensity ultrasound, have been reported to cause membrane rupture and cell lysis, respectively [14, 63]. Inactivation of microbial cells by cell lysis can produce additional beneficial effects, the contact between the released molecule and the host cells is improved [36, 40], increasing chances of MAMP-PRR interactions which are important for eliciting immunological responses, making ghost probiotics attractive than probiotics.
Misuse of antimicrobials in agriculture and medicine has resulted in development of antimicrobial-resistant microbes in animals. And also, interaction of microbes in gut might result in acquisition of antibiotic resistance and virulence genes in strains that previously lacked these through horizontal gene transfer. Alarmingly, antibiotic-resistant
Industrial processing and storage of probiotic products present viability and stability challenges, probiotic cultures should remain viable and sufficient numbers must reach the target site after thermal processing, storage, and gastrointestinal transit. To avoid these technological challenges, ghost probiotics are used. The dead inactivated cells, ghost probiotics do not require refrigeration to maintain the cultures in a stable and viable state. This reduces the cost of storing and transporting ghost probiotics, allowing them to be used by the poor in impoverished locations such as rural areas where refrigeration machines and facilities are lacking. [14], making them a cheaper and accessible option than probiotics.
Remarkably, ghost probiotics can remain stable in extreme environmental conditions, like water activity (Aw), temperature and pH which are considered stressful to probiotics and they have a longer shelf life. In addition, they can be supplemented into foods, other than dairy products like fruit juices and other cereal products [14], thus provide beneficial effects to lactose intolerant individuals. The heat-inactivated
Ghost probiotics, being dead and inactive cells, are unable to create metabolites such as bacteriocins, lactic acid, vitamins, and enzymes that are essential for probiotic health effects [14]. Additionally, the chemical mechanism of action of ghost probiotics is unknown; nevertheless, cell wall polysaccharides, peptidoglycans, surface proteins, and teichoic acids are known to activate immunological responses. Unlike postbiotic components which exist in purified form, ghost probiotics mechanism of action is unclear and is difficult to point out which molecule does what due to complex bacterial architecture [36]. Some methods of microbial inactivation such as thermal treatment affect the physiological activity of the resulting dead cells and the stability of their beneficial effects during shelf life, resulting in altered and non-identical biological responses [14, 36]. For instance, heat treatment at 121°C for 15 minutes of multispecies of lactic acid bacteriaie.,
Their side effects have not been fully understood. Studies have been done on how the microbiome of the gut reconstituted itself after antimicrobial treatment with and without ghost probiotic administration [68]. This means the impact ghost probiotics can have in the medical industry is questionable. There is an issue of, what is being studied is not exactly what would be administered to people [69]. For instance, when research is being carried out it involves a specific organism defined by genus, species and strain (these are pure and carefully dosed). But when buying off the shelf mixed with other products such as food products, people become skeptical about what they are getting dosage wise [70].
Research being carried out is claimed to be of low quality, small in size and often funded by companies with significant conflicts of interest [71].
The inactivation method of ghost probiotics functions can interrupt the bacterial cells and allow for an interface between intracellular bioactive compounds and the host cells on the administration of ghost probiotics. Delivery and formulation of ghost probiotics has been limited in the clinical field [31].
In light of the safety and technological challenges associated with probiotics [14, 40], use of ghost probiotics will expand in near future. Therefore, there is an urgent need to clarify several points to support regulatory authoritiesin defining the requirements for the registration and approval of functional foods containing ghost probiotics and those that have health claims to protect consumers. There is currently an overlap of terminology in defining the biotics terms, ghost probiotics and post biotics which makes communication difficult among researchers, manufacturers, and customers [14]. Therefore, there is a need for internationally recognized clear-cut definitions to avoid confusion that currently exists in biotics, especially for probiotics, postbiotics and ghost probiotics [14]. As result of this mayhem, the ghost probiotics are currently marketed as probiotics [72]. Chiefly, ghost probiotics production, detection, and quantification methods need to be look into closely [14] and standardized [14], before regulations and/or requirements are laid out and implemented. The FDA should then layout the ghost probiotics specific requirements and specifications to iron out the mix-up.
Global commercialization of ghost probiotics is also one of the issues recognized from a regulatory view point because of the geographical differences, for example some traditional probiotics are classified differently across countries like Generally Regarded As Safe for USA and QPS for Europe and additionally some probiotics do not follow the same regulation globally. The regulatory process followed so as to launch a non-traditional probiotic is as complicated as one required for drugs [73].
The current regulations on probiotics are inadequate to protect the consumers and the prescribing doctors, there is abuse of the word probiotics and no specifics of microorganism are indicated in products [74]. Obviously, just like probiotics, ghost probiotics cannot be approved as drugs, even though they are sometimes used for the prevention, management or treatment of disease [75]. In the United States, and many regions of the world, probiotic products are marketed as dietary supplements (not drugs) and are therefore subject to different manufacturing and quality control standards than approved drugs are [75, 76], the same should apply to ghost probiotics. Exemption should be given to ghost probiotics with health claims, these should be treated aspharmaceutical products and regulated as such [75]. To assure safety to end-users, pharmacists should be aware of product quality when recommending these dietary supplements to risk populations like immunocompromised individuals [75] and infants and manufacturing quality control standards should be steeper especial for this vulnerable group [40].
Additionally, manufacturers should be in a position to provide evidence of quality criteriawhen required to and they should guide pharmacists on the safe use of specific products [75]. Manufacturers should have quality management systems in place, and third-party and/or regulatory organizations should verify compliance. Accordingly, the regulatory aspects that need to be considered for ghost probiotics are efficacy, safety, andquality control of manufacturing.
There is a need for large randomized placebo-controlled single strain trials with standard dosing, formulation and duration of treatment in various diseases to get consistent results. At this moment it is difficult to recommend any particular ghost probiotic for a particular disease as the preparation and dosing may not be available commercially. The interaction of the gut microbiota with its host and mutual regulation has become one of the important topics of biomedical research. Their relevance in human diseases require much more research. The popularity of ghost probiotics is fast increasing shortly they will be used in food, medicine, and agriculture. Additionally, the diet microbiota host interface can give rise to newer therapeutic approaches based on selective alteration of microbial metabolite production to support human health and prevent diseases. The metabolic profiling approach, suggests how mining the microbiota may lead to personalized treatment.
The authors declare no conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors"},{id:"17",title:"Metabolism",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation"},{id:"18",title:"Proteomics",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/288201",hash:"",query:{},params:{id:"288201"},fullPath:"/profiles/288201",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()