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.
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We 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!
IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\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\n
We 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!
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1. Introduction
Ruminants can eat different types of feed that are digested by microbial biomass resulting in better metabolism, which ultimately impacts the dairy animal productivity. The microbial flora in the gastrointestinal tract (GIT) has a major impact on the productive efficiency, health status, and well-being of the dairy animals [1–3]. The diversity and function of ruminal GIT microbes are very important in feed digestion. The way the nutrients are digested in GIT in ruminants have a crucial impact on growth, health, and productivity [4]. The GIT inhabits multifarious microbial diversity that helps in generating impassive response regarding nutritious health, physiology, and productivity of animals [1]. The existing gut microbiota regulates food safety through the shedding of pathogens, interaction with organisms and resource competition in the GIT [5]. Gastrointestinal tract microflora aids in stimulation of the immune system that acts as a barrier against infectious pathogens. It also restrains the injurious and pathogenic bacteria in gut colonization [6]. Different strategies have been used to enhance the microbiota of gastrointestinal tract, which ultimately affect the production potential and growth efficiency of dairy animals. Nowadays, the improvement of microbiota of the gastrointestinal tract by using probiotic has become a useful and economical method to enhance the health and productive performance of animals. A live microorganism which beneficially influences the host by improving microbial flora of its intestine is called probiotic [7]. Numerous microorganisms have been sanctioned as probiotics that are used in diet of ruminants to upgrade nutrient utilization and animal performance [8]. Bacterial probiotics give better results in young calves, chickens, and pigs, whereas yeast/fungal probiotics are effective in adult ruminants [9]. During the last decades, Saccharomyces cerevisiae have been used as preventer supplement against diarrhea and other digestive system problems in livestock [10]. They also give production benefits, reduced digestive problems, and better health of animals in cost-effective manners [11]. Dietary supplementation of yeast culture has a positive effect on feed intake, which ultimately enhances ruminant growth [12] and production efficiency [13]. It also has positive effect on milk fat content [13–15] and milk urea nitrogen [16]. Moreover, it decreases lactate production [17], increases desirable bacterial population [13], prevents the rumen acidosis [18], increases the hemicelluloses degradability, and some important nutrient (NDF, ADF) digestibilities [19–21]. Another advantage of use of the S. cerevisiae is that the benefit to cost ratio of S. cerevisiae supplementation in dairy cattle is 4:1 [22]. This chapter explains the yeast effects on the ruminants and proposes guidelines to develop the breed specific probiotic yeast for animal use.
2. Probiotic yeast
Yeasts are eukaryotic microorganisms and are different from bacteria from the structure and functional aspects [23]. Yeasts are facultative anaerobes and differ in terms of their location, shape, reproducing activities, subtracts they utilize and are highly resistant to different antibiotics, such as sulfamides and other antibacterial substrates [24]. The resistance capability of the yeast cells is natural and genetically encoded. This resistance cannot be changed or transmitted to other microbial species. The size of the yeast cell (5 × 10 μm) is also higher than bacteria (0.5 × 5 μm). The study of antagonistic yeast to block bacterial pathogenicity in the early stage of development is mainly due to following steps; (1) competition for nutrients, (2) pH changes in the medium, (3) high concentrations of ethanol production, (4) secretion of antibacterial compounds and release of antimicrobial compounds (toxins or “mycocins”). However, the effectiveness of probiotic organism is viewed as population-specific due to variation in gastrointestinal microbial flora, feeding habits, and precise interaction between host animal and microbes. As most of the probiotic yeast strains accessible in the market are of Western or European origin, hence, there is a dire need to explore new indigenous probiotic strains. Yeast cells produce many important fermentation metabolites and different types of important minerals and enzymes that make it useful and highly nutritive feed supplement for ruminants [25–27]. It also provides improved production, reduced digestive problem, and better health in cost-effective manners.
3. Understating the ruminal gut microbiology for development of new target-specific probiotic strain
Uses of molecular techniques have changed the study of the rumen ecosystem [10]. A better understanding of the rumen microbiology is an important step to select and prepare a new yeast strain affecting on functional-specific microbes. Ruminants’ stomach consists of reticulum, rumen, omasum, and abomasums [28]. The rumen is an anaerobic chamber that harbors an immense diversity of microbial community including bacteria, archaea, fungi, and single-celled ciliated protozoa (Figure 1) [29].
Figure 1.
Estimated rumen microbial ecosystems.
This microbial ecosystem has been used for better feed digestion. Bacteria are numerous microbes in rumen [30]. Mostly bacteria are associated with feed; some are free living, attached with mucous membrane and associated with fungi and protozoa. The shape of rumen bacteria are mostly cocci, rod spirochete budding, and filamentous. Rumen bacteria are 1–2 μm in size. The majority of the rumen bacterial species are Gram-negative. The structure of this microbial community is influenced by many factors, including host species, age, seasons [31], type of feed, geographical location, and whether the animal has received any treatment [32]. The balance in rumen microbial flora plays a crucial role in feed utilization and could result in better productivity [33]. The rumen microbial profile directly depends on the type of feed [29]. Ruminants can eat from different types of feed sources that are digested by microbial biomass, which helps in better metabolism [34]. This ultimately impacts the productivity of dairy animals. The feed microbial flora could be managed by using beneficial microbial supplementation. The management and modification of ruminal fermentation to improve animal performance have been the main objective of several studies on ruminant species. From this line of research, we will use method to manipulate the rumen fermentation for improving nutrient utilization and productivity of animals. The banning of the use of antibiotics as animal growth promoters in the European Union in 2006 has increased the demand from producers for alternative feed additives that can be used to manipulate the ruminal fermentation and improve animal production [31, 35, 36]. The modulation in the rumen population for better nutrients metabolism can be achieved made by manipulating the feed, antibiotic and some microbial inoculants. The diet-shift effect such as high-forage diet, increases the rumen pH and consequently improves the stability and viability of cellulolytic and hemicellulolytic bacteria and protozoa. On the other hand, high-concentrate diet that decreases the rumen pH, resultantly decreases the cellulolytic and hemicellulolytic bacteria and increases the amylolytic bacteria and lowers the rumen protozoa. Microbial inoculants may alter the stability and viability of microbial population of the rumen and hindgut in a better way.
4. Role of probiotic yeast in ruminant nutrition
The balance in rumen microbial flora plays a crucial role in feed utilization and could result in better animal productivity [37]. Several hypotheses concerning the mode of action of probiotic yeast in animal nutrition have been proposed; however, a majority of them emphasize positive effects by modifying rumen microbial population. The first and most widely supported mode of action is that the yeast stimulates the growth of bacteria (cellulolytic, amylolytic, and proteolytic) and protozoa [38, 39]. The rumen dissolved oxygen (O2) can be measured in situ [40]. Loesche [41] found that a majority of rumen microbial flora are highly sensitive to O2. Probiotic yeasts remove oxygen from rumen and provide a better anaerobic environment for bacterial growth [42]. Sixteen liters of oxygen can enter inside rumen daily, by the mean of feeding, rumination, and salivation [43]. Inside rumen, yeast cells use oxygen for their metabolic process. Freshly ingested feed particles have sugars and small oligosaccharides. Probiotic yeast metabolizes these small particles and produces peptides, polypeptides, and amino acids. This respiratory activity of probiotic yeast lowers the oxidation-reduction potential inside rumen [44]. A negative change in the redox potential (−20 mV) has been observed in rumen with probiotic yeast addition [36]. This change gives a better anaerobic condition inside rumen [33]. Aforementioned environment helps in the protection of rumen bacteria from damage by oxygen and stimulation of growth of cellulose degrading bacteria [45, 46]. These conditions will also be helpful in the cellulose degrading process (cellulose digestion). Respiratory-deficient mutants of probiotic yeast cannot stimulate bacterial growth. As we mention earlier that O2 scavenging property of yeasts is very important for growth of rumen microbial biomass, hence, this O2 scavenging property should be considered when probiotic yeast is selected for ruminants (Figure 2).
Figure 2.
Representative scheme of effect of live yeast on the microbial flora of the gastrointestinal tract in ruminants: the probiotics yeast can improve the composition of the intestinal microbiota through the production of antimicrobial substances which inhibit the pathogenic bacteria ultimately improving the gut health. Although there is a difference between the probiotic colonization microbiota and the target rumen microbiota, many researchers suggested that there is a relationship between the GIT microbiota and other tissues of the host body.
Probiotic yeasts have beneficial effects on the lactate-metabolizing bacterial species. S. cerevisiae provides different growth factors essential for the growth of lactic acid fermenting bacterial species, such as Megasphaera elsdenii or Selenomonas ruminantium. In dairy animals, a reduction of lactic acid concentration was seen inside the rumen with live yeast addition (Figure 3).
Figure 3.
A scheme describing the mode of action of yeast culture. Adopted from Ref. [21].
4.1. Role of probiotics in the establishment of rumen and hindgut micro-flora establishment
The key of the rumen development is to provide supporting conditions to the microbiota to ensure its optimal establishment. It has been well studied that live yeast can help in establishing different types of micro-flora in neonate by positively modulating rumen colonization, by important functional microbial population. A newborn ruminant digestive system is sterile but with passage of time when they contact with their mother and other animals, they get microbes from their saliva and feces [10]. In contrary, the mother and her young connection are more common in small-scale farming systems. On the other hand, in intensive dairy farming systems, the neonate is alienated from the mother and is fed on solid feeding that provides a negative situation in the development of rumen microflora [47]. The early maternal separation has a negative effect on the rumen colonization by important microbial species. This negative situation leads to poor rumen microbial development making the neonate to suffer from different digestive diseases like diarrhea. Different diseases of digestive system are most important factors of low income heifers rearing. It has been well studied that live yeast culture can help the establishment of key microbial communities (Bacteroides-Prevotella and Clostridium coccoides-Eubacterium rectale group) in neonate by removing the oxygen from rumen. The rate of cellulose degrading microflora population was greater in lambs fed on S. cerevisiae addition as compared to the control [10]. Live yeast could be used as a nutrition tool for maturation of the rumen microbial ecosystem, which can result in a positive effect on animal performance, and health both before and after weaning, with an increase in grain intake and reduced frequency of diarrhea. S. cerevisiae had the ability to provide different types of organic acids or vitamins, those stimulating ruminal populations of cellulolytic bacteria and lactic acid utilizing bacteria (LUB) [48]. The cellulose degrading microbial population was also much stable in the animals fed on yeast addition because protozoa comes in rumen only once the bacterial species are present inside the rumen. It has been also noted that protozoa appeared earlier in those animals who fed on S. cerevisiae addition [49]. Amylolytic bacterial population is also affected by yeast in the rumen [38]. It is because the protozoan concentrations are proliferated and are able to store starch and postpone bacterial fermentation [50]. Proteolytic bacterial activity was highest in the yeast supplemented animals. Proteins in the feed are quickly broken down into peptides, amino acids and ammonia (NH3) by different protozoa and fungi inside rumen [51]. Some NH3 is converted into microbial protein (MP) and some ammonia is used by the animal in the form of urea. An important portion of rumen ammonia is excreted and represents an indication of nitrogen (N) loss of the dietary nitrogen intake (20–25%) [30]. Amino acids and peptides issued from dietary proteins cannot be directly slipped in the animal intestine, if the diet has highly nutritious value. The same effect on ammonia concentration was observed with daily yeast culture supplementation in adult ruminants [52]. In vitro findings tell that probiotic yeast could alter the growth and activities of protein-degrading bacteria, which ultimately enhanced the protein digestion inside rumen [53]. The mode of action of yeast can be explained by a fight between live S. cerevisiae cells and different bacterial species for energy utilization [54]. A study on 14 dairy cows field trials addition of yeast strain in the diet revealed that the soluble nitrogen of the diet was a key factor to drive the production parameters to the probiotics yeast [55]. However, with other yeast strains, no significant effect was observed on the concentration and fraction of microbial nitrogen in dairy cattle [56]. Further study is needed to investigate the effect of probiotic yeast on the nitrogen microbial metabolism [10]. Many studies have shown that increased feed intakes are driven by increased flow of absorption nitrogen [43, 57]. This step stems simultaneously from the proliferation and stimulation of viable cell counts of anaerobic bacteria population. A higher ammonia nitrogen concentration measured for vessel in which live yeast was added compared to autoclaved yeast suggest that, the live yeast stimulated the proteolytic activity of the rumen bacterial species that ultimately influenced rumen fermentation [58]. It was noted that digestibility of crude protein was significantly higher in animals fed on the mixed fungal (yeast and Aspergillus) supplementation and it is suggesting that fungal supplementation might promote proteolytic activities by supplying some types of stimulatory factors [59]. Many studies have shown that animals fed on the yeast supplementation have been associated with higher concentration of ammonia nitrogen, which might suggest that proteolytic bacterial activity has been stimulated by yeast culture [60, 61]. The second proposed mechanism is that yeast cell provides the soluble growth factors such as, organic acids, branched-chain volatile fatty acids, vitamins, and amino acids, which have a positive effect in stimulating cellulolytic, proteolytic and lactic acid utilizing bacteria [59, 62].
4.2. Effect of yeast and yeast cultures on rumen fiber digestion
Fiber is non-digestible polysaccharides (a complex form of carbohydrate) [63]. In nutrition, the term fiber defines as a component of plant that is not digestible by mammalian enzyme [64]. Cellulose, hemicellulose, and lignin are the primary components of fiber. Cellulose and hemicelluloses constitute 15–70% of most ruminant diet [65]. Cellulose is the most abundant carbohydrate in plant cell wall. Chemically, cellulose is made up of linear chains of sugar molecules. In cellulose, glucose molecules are linked together in a β-1,4 links, and this linkage can only be digested by microbial cellulolytic enzymes (Table 1).
The effects of various probiotic yeast strains on ruminant performance.
Cellulose makes up about 40% of plant cell walls. Hemicellulose also can only be digested by microbial enzymes because it also has β-1,4 linkages. Hemicellulose has a strong negative effect on fiber degradation because of close association with lignin [66]. The rumen is an important part of the ruminant’s stomach because cellulose is broken down into simple sugar that can be used by the animal body inside rumen. The rumen represents a mobile, self-sustaining fermentation system for plant material [67, 68]. It is a complex microbial ecosystem that contain many types of microorganisms such as, bacteria (1010–1011 cells per ml), protozoa (104–106 per ml) and fungi species (103–105 zoospores per ml) [69, 70].
4.2.1. Rumen fibrolytic bacteria
Rumen bacteria (1011 viable cells per ml) dominate the fermentation, both in terms of numbers and metabolic processes. The rumen bacteria are 99.5% obligatory anaerobic. In rumen, 200 species with many subspecies of bacteria are present. There are different kinds of bacteria in the rumen, which aid in fermentation process [71]. Fibrobacter and Ruminococcus are the main rumen fibers degrading bacteria in cattle [72, 73]. Fibrobacter succinogenes is a Gram-negative and rod-shaped anaerobe first isolated from the cattle [74]. Despite their important role, cellulose degrading bacteria are argued to only comprise of 0.3% of the total bacteria population inside rumen [75]. Rumen bacteria are classified into fibrolytic, amylolytic, pectinolytic, proteolytic, lipolytica, lactate using bacteria and hydrogen-using bacteria. Amylolytic bacteria ferment starch while fibrolytic bacteria involve in the fermentation of fiber. Different bacterial populations dominate the rumen fermentation depending on the type of feed. Cattle that are fed on high-fiber diet will have a ruminal bacterial population that is high in fibrolytic bacteria especially Ruminococcus ssp. Rumen bacteria are mainly involved in the fermentation of fiber, starch, and sugar in the feed.
4.2.2. Rumen fibrolytic fungi
Ruminal anaerobic fungi, an emerging group of animal probiotics, account for approximately 8% of the total rumen microbial biomass in ruminants [76]. Rumen fungi have a crucial role in the degradation of fiber material [77–80]. The fungi have an important role in fiber digestion because of the vegetative thallus rhizoids. The rhizoids have a more penetrating capability to plant cell wall as compared to the bacteria and protozoa. Degradation of lignin of the plant cell wall is a main characteristic of rumen fungi [81, 82]. Fungi degraded 37–50% of barley straw. The fungi fibrolytic activity enhanced by hydrogen-utilizing methanogens decreases the cruel effect of hydrogen [76, 83]. Fungi play an active and significant role in fiber digestion of low quality roughages by breaking the beta-1,4 linkages between lignin and hemicelluloses inside the plant cell [84]. Fungi have a positive role in fiber degradation as evidenced by producing a wide array of potential hydrolytic enzymes [79, 85, 86].
4.2.3. Rumen protozoa
In vitro studies have suggested that 19–28% of the total cellulosic activity in fiber digestion can be attributed to protozoa [87]. However, digestion seems to be limited to very susceptible tissue, for instance, mesophyll cells [88]. Studies have demonstrated that defaunation (removal of protozoa) reduces the rate of fiber/cell wall degradation digestion [89, 90]. However, in the absence of protozoa, there is an increased requirement for non-protein nitrogen (NPN) because of an increased bacterial population. A reduction of N may therefore result in the reduction in fiber digestion [91].
4.3. Mode of action of probiotic yeast in the post-ruminal GIT
The GIT inhabits multifarious microbial diversity that helps in generating impactive response regarding nutritious, health, physiology, and productivity of animals [1]. The existing gut microbiota regulates food safety through shedding of pathogens, interaction with organisms, and resource competition in the GIT [5]. The physiological, anatomical, and immunological status of the host is strongly dependent upon microbiota of GIT which facilitates essential functions to host. GIT microflora aids in the stimulation of immune system that acts as a barrier against infectious pathogens. It also restrains the injurious and pathogenic bacteria gut colonization [6]. The microflora that resides in GIT mostly belongs to Bacteroides, Bifidobacterium, Clostridium, Eubacterium, Fusobacterium, and Lactobacillus families. Among all of the intestinal microbiota, Enterococcus and Escherichia coli represent the least contribution (upto 1%) whereas, anaerobes show dominancy over microaerophiles and facultative anaerobes by 1000:1 [92]. Lactobacillus and Bifidobacteria are marked as predominant flora which counts for 90% of the total population in GIT. The fluctuating flora represents their existence in trace, i.e., less than (0.01%) that is usually considered as more diversified and pathogenic ones [93]. The GIT microbiota protects the host from pathogen, which produces digestive diseases like diarrhea. The performance of the calf is directly related to the efficient growth along with the improved health status [94]. Gut microbial flora play an important role in the growth and health of the animal. Probiotics put beneficial effects on the health of gut by improving its microbial balance. They have antidiarrheal capability and enhance the growth performance of animals [94, 95]. The intestinal microbiota of cattle performs its vital role in the fermentation process. They help in methane emission by means of fermentation both from rumen and large intestine [96]. The microbial diversity in the GIT of the dairy cattle has lot of impact on the productivity and well-being of the cattle [1–3, 97]. There is no direct evidence that yeast or fungal extracts affect digestion or metabolism in the lower gut. However, the potential for such effects should not be ignored [98]. This improvement can be due to either the effect of mannan-oligosaccharides (MOS, a component of yeast cell wall) on the immune modulation or direct effect of yeast on the reduction of pathogenic bacteria and toxic metabolites. According to the findings of Heinrichs et al. [99], MOS has an ability to bind selected pathogen by blocking the microbial lecithin and preventing the pathogens from colonization in host GIT. As noted, previous inquiries regarding feeding direct fed microbial products (DFM) to ruminant animals focused on its potential beneficial effects on the post-ruminal GIT (Figure 4).
Figure 4.
Simple scheme proposed to explain mode of action of probiotic yeast in rumen and post-ruminal GIT: live yeast improves carbohydrates, protein, and lipid digestion rate by improving the production of cellulolytic, hemicellulolytic and proteolytic, and lipolytic bacteria and fungi.
5. Experimental proofs
5.1. Experiment 1: effect of probiotic yeast on the growth performance and fecal biomarkers of dairy heifers
Poor growth performance in growing animals is associated with imbalanced nutrition. The use of probiotic yeast would minimize the expenditure of replacement heifers with optimum growth rate. In our experiment, young animals fed on the diet supplemented with yeast culture gain more weight than non-supplemented animals. In this experimental study, eight dairy heifers (87 ± 5 kg and 6–7 months) were divided into two equal groups of four animals each (control and probiotic) following completely randomized design [100]. During the trial, heifers in control group were offered control diet (NRC recommended diet), while in the probiotic group fed with control diet plus commercial available probiotic yeast (Yea-Sac1026; 5 g/animal) for a period of 120 days. Results reveal that dairy heifers fed on the probiotic feed gained significantly (P < 0.05) higher average weights than dairy heifers fed on control feed (Figures 5 and 6) [34].
Figure 5.
Average monthly dry matter intake pattern (kg) of dairy heifers fed on control feed (control, ♦; no yeast) or commercial probiotic feed (COM-P, ■; control feed plus commercial yeast).
Figure 6.
Average monthly growth pattern (kg) of dairy heifers fed on control feed (control, ♦; no yeast) or commercial probiotic feed (COM-P, ■; control feed plus commercial yeast).
Probiotic yeast decreases the pathogenic bacteria and increase the beneficial bacteria in present study (Figure 7) [34].
Figure 7.
Total E. coli and Lactobacillus count (CFU/g) in the ruminal gut of dairy heifers fed on control feed (control, ♦; no yeast) or commercial probiotic feed (COM-P, ■; control feed plus commercial yeast).
5.2. Experiment 2: development of indigenous probiotic yeast for local breed
From the aforementioned discussion, we found that an important step to establish a breed probiotic strain is that the origin of the isolated strain should be animal based for their better adhesion and colonization in the animal GIT. We hypothesize that, breed-specific probiotic yeast gives better results in terms of milk production. From this line of research, we conduct an experimental study to develop the indigenous probiotic yeast for local breed and to evaluate its effect on the lactating animals. A S. cerevisiae strain was isolated from dung samples of the dairy animals. After careful assessment of its probiotic test, that yeast strain (animal probiotic) was further used in same dairy cattle feed (Figure 8) [100].
Figure 8.
Flow sheet of development of indigenous probiotic yeast for local breed.
5.3. Experiment 3: impact of indigenously isolated Saccharomyces cerevisiae probiotics on milk production and gut microbial species of lactating cows
Nine lactating dairy cattle of mix breed (Sahiwal and Sahiwal × Jersey) at their first and second lactation (producing 4–5 l/day) were used for the experiment. Cows were fed a concentrate feed, maize silage, and oat fodder. The neutral detergent fiber digestibility was improved in the presence of 3.13 × 1007 CFU/g of our laboratory produced live yeast and milk production was improved by 0.7 kg/d in the laboratory produced probiotic fed dairy cows (Figure 9).
Figure 9.
Effect of yeast on milk yield (Means ± SEM) in lactating dairy cattle fed on the diet supplemented with no yeast (control, ♦), laboratory yeast (LAB-Y, ■) or commercial yeast (COM-Y, ▲).
We assumed that improved performance is might be due to cellulolytic activity of the S. cerevisiae which was isolated from dairy animal dung sample [101]. This activity enhanced the cellulose digestion rate and helped in the milk synthesis [14].Yeast culture significantly (P < 0.05) increased the fiber digestibility, resulting in an increased supply of absorbed nutrients for milk synthesis in our experiment [101]. Results of the ruminal gut microflora showed that the average beneficial Lactococcus species (CFU/g) counts were increased while pathogenic Enterococcus species (CFU/g) counts were lower in laboratory produced yeast (LAB-Y) fed lactating cows than other groups which lead to improve GIT microbial balance. The economic efficiency of LAB-Y fed group that was 4.7% better than the control group, fed no yeast culture. It can be concluded that indigenous isolated probiotic yeast strain improves the production performance, gut health, and well-being of lactating dairy cattle in cost-effective manner. Locally isolated yeast strain may be adopted well in the cattle gut than exotic probiotics [100].
6. Challenges in preparation of suitable probiotics yeast
Traditionally, as ruminates live in different parts of the world, hence, different yeast strains may exhibit different effects upon the ruminal fermentation depending on their location. Therefore, we should identify new yeast strains for getting best results for the rumen fermentation in their own living condition. For getting positive results in the ruminants, probiotic strains should be breed specific. Latest knowledge related to modes of action of probiotic yeast and its beneficial effects on rumen fermentation, may aid in selection of new breed-specific strains which act on specific key target microorganisms (Cellulolytic, hemicellulolytic bacteria and fungi) and areas of rumen fermentation. Inside the rumen fluid, certain probiotic yeast candidate cannot remain active for longer periods of time. On the other hand, probiotic strains viability and stability are the more advanced technological challenges faced by the livestock industry holders. There is a strong interaction between the host animal and microbial population. To overcome these challenges, further empirical studies are needed on the study of probiotic candidates as well as the ruminal gut microbiota activities to enhance the information of the host-specific interactions. Then the goal is to apply the knowledge of ruminal gut health normal microbial species composition in comparison with microbiota present during disease to select the right breed-specific probiotic strain (Figure 10).
Figure 10.
Challenges in preparation of suitable probiotics yeast.
7. Conclusions and future research
Probiotic supplemented animal feed has promising effects on the remains to a bright livestock industry future. However, formulating the cost-effective bioactive feed for the dairy animals is remaining as the main challenge faced by the rumen microbiologist. In this regards, search for novel probiotic strains will be the key research and development spot for future livestock markets all over the world. The target oriented applications of specific strains may have huge potential application in treating many chronic disorders in animals. This would lead to have more economical and biological farming. The probiotic strains of same ecological origin may be more compatible with rumen micro-biome fielding maximum outputs. Therefore, the future feed supplementation may be of breed specific. Recently, consumer’s demand about safe and healthy food products has been increased worldwide. Hence, the advantage of using probiotics is not only to enhance the productive performance but also to (contribute to) lower the risk of ruminant GIT carriage of human pathogen and to reduce excretion of polluting outputs such as nitrogen-based compounds and methane. The S. cerevisiae received the Generally Recognized as Safe (GRAS) status from Food and Drug Administration (FDA) and thus, is appropriate for use in animal feeds. Some factors, such as, expected response, net profit, ongoing research, and field responses should be considered to determine when a feed additive is used for experiment. Fermented yeast culture has emerged as a cost-effective product that has many benefits to ruminants. One of the major benefits of the probiotic yeast is that yeast has no antibiotic resistance gene. It also has ability to colonize in the GIT, to neutralize enterotoxin, and to tolerate bile salt and gastric acid, resultantly improving the health status and production efficiency of the dairy animals. Normally, the feed cost is high, however, probiotic yeast gives a useful nutritional strategy which provides increasing diet digestibility and consequently enhances the performance parameters of the dairy animals in cost-effective manner. Future experimental studies are needed to investigate the impact of the yeast cells in the GIT of the dairy animals. The future research will also need to address the behavior of the yeast cells in the digestive environment. We look forward to the development of the new breed-specific probiotic strains, which will hopefully mean that the rumen microbiologist instead of following the nutritious in an exploratory mood as has been the role for so long, will instead lead advances in ruminant nutrition in the year to come.
8. Recommendations
The recommendations are outlined as follows:
Isolation of new indigenous bacterial and yeast strains.
Study the probiotic characterization and genetic potential of the probiotic strains.
Complete nutritional profile of the probiotic strains for preparation of probiotic feed.
Application of probiotic strains for more milk and meat production of local breed animals.
Amino acid profile of the milk of dairy animals fed on the probiotic feed.
\n',keywords:"indigenous probiotics, viability, stability, gastrointestinal tract, rumen microbiota",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/57290.pdf",chapterXML:"https://mts.intechopen.com/source/xml/57290.xml",downloadPdfUrl:"/chapter/pdf-download/57290",previewPdfUrl:"/chapter/pdf-preview/57290",totalDownloads:2235,totalViews:1030,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,dateSubmitted:"November 23rd 2016",dateReviewed:"September 1st 2017",datePrePublished:null,datePublished:"November 8th 2017",dateFinished:null,readingETA:"0",abstract:"The main purpose of yeast supplementation is to treat rumen microbial dysbiosis which may enhance the nutrient utilization leading to enhanced animal growth and productivity. Yeast improves rumen ecosystem by two ways: by direct production of digestive enzymes and growth stimulator and by promoting the growth and function of beneficial microbiota. Yeasts have potential to produce metabolites, which stimulate the growth, like rumen acetogens and antimicrobial compounds which inhibit potential pathogens. The yeast probiotic impact on animals depend on different interacting factors including animal breed, supplemented dose, type, diet, strain, physiological stage and feeding system. In the situation of a high feed cost all over the world, probiotic yeast gives a useful nutritional strategy which allows increasing diet digestibility and consequently enhances the performance in ruminants in cost-effective manner. Many yeast culture-based products are commercially available worldwide, but their effectiveness as probiotic dietary supplement in a particular breed is mostly questionable. Therefore, exploration of the new indigenous probiotic strain is of great interest in this context. The probiotic strains of same ecological origin may be more compatible with rumen microbiome giving maximum outputs. Moreover, the breed specific probiotic yeast is an economical and viable option for farmers to overcome the effects of malnutrition.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/57290",risUrl:"/chapter/ris/57290",book:{slug:"yeast-industrial-applications"},signatures:"Shakira Ghazanfar, Nauman Khalid, Iftikhar Ahmed and\nMuhammad Imran",authors:[{id:"202370",title:"Dr.",name:"Shakira",middleName:null,surname:"Ghazanfar",fullName:"Shakira Ghazanfar",slug:"shakira-ghazanfar",email:"shakira_akmal@yahoo.com",position:null,institution:{name:"Quaid-i-Azam University",institutionURL:null,country:{name:"Pakistan"}}},{id:"203378",title:"Dr.",name:"Muhammad",middleName:null,surname:"Imran",fullName:"Muhammad Imran",slug:"muhammad-imran",email:"m_imran766@hotmail.com",position:null,institution:null},{id:"203379",title:"Dr.",name:"Iftikhar",middleName:null,surname:"Ahmed",fullName:"Iftikhar Ahmed",slug:"iftikhar-ahmed",email:"iftikharnarc@hotmail.com",position:"Principal Scientific Officer / Director (IMCCP)",institution:null},{id:"203380",title:"Dr.",name:"Nauman",middleName:null,surname:"Khalid",fullName:"Nauman Khalid",slug:"nauman-khalid",email:"nauman_khalid120@yahoo.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Probiotic yeast",level:"1"},{id:"sec_3",title:"3. Understating the ruminal gut microbiology for development of new target-specific probiotic strain",level:"1"},{id:"sec_4",title:"4. Role of probiotic yeast in ruminant nutrition",level:"1"},{id:"sec_4_2",title:"4.1. Role of probiotics in the establishment of rumen and hindgut micro-flora establishment",level:"2"},{id:"sec_5_2",title:"4.2. Effect of yeast and yeast cultures on rumen fiber digestion",level:"2"},{id:"sec_5_3",title:"4.2.1. Rumen fibrolytic bacteria",level:"3"},{id:"sec_6_3",title:"4.2.2. Rumen fibrolytic fungi",level:"3"},{id:"sec_7_3",title:"4.2.3. Rumen protozoa",level:"3"},{id:"sec_9_2",title:"4.3. Mode of action of probiotic yeast in the post-ruminal GIT",level:"2"},{id:"sec_11",title:"5. Experimental proofs",level:"1"},{id:"sec_11_2",title:"5.1. Experiment 1: effect of probiotic yeast on the growth performance and fecal biomarkers of dairy heifers",level:"2"},{id:"sec_12_2",title:"5.2. Experiment 2: development of indigenous probiotic yeast for local breed",level:"2"},{id:"sec_13_2",title:"5.3. Experiment 3: impact of indigenously isolated Saccharomyces cerevisiae probiotics on milk production and gut microbial species of lactating cows",level:"2"},{id:"sec_15",title:"6. Challenges in preparation of suitable probiotics yeast",level:"1"},{id:"sec_16",title:"7. Conclusions and future research",level:"1"},{id:"sec_17",title:"8. Recommendations",level:"1"}],chapterReferences:[{id:"B1",body:'Guarner F, Malagelada JR. Gut flora in health and disease. The Lancet. 2003;361:512-519'},{id:"B2",body:'Dowd SE, Callaway TR, Wolcott RD, Sun Y, McKeehan T, Hagevoort RG, Edrington TS. Evaluation of the bacterial diversity in the feces of cattle using 16S rDNA bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP). 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The rumen microbial ecosystem-some recent developments. Trends in Microbiology. 1997;5:483-488'},{id:"B69",body:'Shakira G, Mirza I, Latif A. Scope of common DNA based methods for the study of rumen bacterial population. Bangladesh Journal of Animal Science. 2013;41:141-146'},{id:"B70",body:'Kamra D. Rumen microbial ecosystem. Current Science. 2005;89:124-135'},{id:"B71",body:'Cho SJ, Cho KM, Shin EC, Lim WJ, Hong SY, Byoung RC, Jung MK, Sun ML, Yong HK, Kim H, Yun HD. 16S rDNA analysis of bacterial diversity in three fractions of cow rumen. Journal of Microbiology and Biotechnology. 2006;16:92-101'},{id:"B72",body:'Kobayashi Y, Shinkai T, Koike S. Ecological and physiological characterization shows that Fibrobacter succinogenes is important in rumen fiber digestion – review. Folia Microbiologia (Praha). 2008;53:195-200'},{id:"B73",body:'Kim M, Morrison M, Yu Z. Evaluation of different partial 16S rRNA gene sequence regions for phylogenetic analysis of microbiomes. Journal of Microbiological Methods. 2011;84:81-87'},{id:"B74",body:'Hungate RE. The anaerobic mesophilic cellulolytic bacteria. Bacteriological Reviews. 1950;14:1-49'},{id:"B75",body:'Brulc JM, Yeoman CJ, Wilson MK, Miller ME, Jeraldo P, Jindou S, Goldenfeld N, Flint HJ, Lamed R, Borovok I, Vodovnik M. Cellulosomics, a gene-centric approach to investigating the intraspecific diversity and adaptation of Ruminococcus flavefaciens within the rumen. PLoS One. 2011;6(10):25329'},{id:"B76",body:'Orpin CG, Joblin KN. The rumen anaerobic fungi. In: The Rumen Microbial Ecosystem. London, UK: Elsevier Applied Science Publishers; 1988. p. 129-150'},{id:"B77",body:'Theodorou MK, Longland AC, Dhanoa MS, Lowe SE, Trinci AP. Growth of Neocallimastix sp. strain R1 on Italian ryegrass hay: Removal of neutral sugars from plant cell walls. Applied and Environmental Microbiology. 1989;55:1363-1367'},{id:"B78",body:'Paul SS, Kamra DN, Sastry VRB, Sahu NP, Agarwal N. Effect of administration of an anaerobic gut fungus isolated from wild blue bull (Boselaphus tragocamelus) to buffaloes (Bubalus bubalis) on in vivo ruminal fermentation and digestion of nutrients. Animal Feed Science and Technology. 2004;115:143-157'},{id:"B79",body:'Lee SS, Choi CK, Ahn BH, Moon YH, Kim CH, Ha JK. In vitro stimulation of rumen microbial fermentation by a rumen anaerobic fungal culture. Animal Feed Science and Technology. 2004;115:215-226'},{id:"B80",body:'Thareja A, Puniya AK, Goel G, Nagpal R, Sehgal JP, Singh PK, Singh K. In vitro degradation of wheat straw by anaerobic fungi from small ruminants. Archiver Animal Nutrition. 2006:412-417'},{id:"B81",body:'Mountfort DO, Asher RA, Bauchop T. Fermentation of cellulose to methane and carbon dioxide by a rumen anaerobic fungus in a triculture with Methanobrevibacter sp. strain RA1 and Methanosarcina barkeri. Applied and Environmental Microbiology. 1982;44:128-134'},{id:"B82",body:'Akin DE, Benner R. Degradation of polysaccharides and lignin by ruminal bacteria and fungi. Applied and Environmental Microbiology. 1988;54:1117-1125'},{id:"B83",body:'Joblin K. Physical disruption of plant fibre by rumen fungi of the Sphaeromonas group. In: The Roles of Protozoa and Fungi in Ruminant Digestion. Armidale, NSW: Penambul; 1989. p. 259-260'},{id:"B84",body:'Tripathi VK, Sehgal JP, Puniya AK, Singh K. Hydrolytic activities of anaerobic fungi from wild blue bull (Boselaphus tragocamelus). Anaerobe. 2007;13:36-39'},{id:"B85",body:'Williams AG, Orpin CG. Polysaccharide-degrading enzymes formed by three species of anaerobic rumen fungi grown on a range of carbohydrate substrates. Canadian Journal of Microbiology. 1987;33:418-426'},{id:"B86",body:'Paul SS, Kamra DN, Sastry VR, Sahu NP, Kumar A. Effect of phenolic monomers on biomass and hydrolytic enzyme activities of an anaerobic fungus isolated from wild nil gai (Baselophus tragocamelus). Letters in Applied Microbiology. 2003;36:377-381'},{id:"B87",body:'Gijzen HJ, Lubberding HJ, Gerhardus MJT, Vogels GD. Contribution of rumen protozoa to fibre degradation and cellulase activity in vitro. FEMS Microbiology Letters. 1988;53:35-43'},{id:"B88",body:'Akin DE. Histological and physical factors affecting digestibility of forages. Agronomy Journal. 1989;81:17-25'},{id:"B89",body:'Bonhomme A. Rumen ciliates: Their metabolism and relationships with bacteria and their hosts. Animal Feed Science and Technology. 1990;30:203-266'},{id:"B90",body:'Yang CM, Varga GA. The effects of continuous ruminal dosing with dioctyl sodium sulphosuccinate on ruminal and metabolic characteristics of lactating Holstein cows. British Journal of Nutrition. 1993;69:397-408'},{id:"B91",body:'Ushida K, Jouany JP. Effect of defaunation on fibre digestion in sheep given two isonitrogenous diets. Animal Feed Science and Technology. 1990;29:153-158'},{id:"B92",body:'Mestecky J, Russell M. Passive and active protection against disorders of the gut. Veterinary Quarterly. 1998;20:83-87'},{id:"B93",body:'Tournut J. The digestive flora of the pig and its variations. Recueil De Medecine Veterinaire. 1993;169:645-652'},{id:"B94",body:'Soberon F, Raffrenato E, Everett R, Van Amburgh M. Preweaning milk replacer intake and effects on long-term productivity of dairy calves. Journal of Dairy Science. 2012;95:783-793'},{id:"B95",body:'Donovan D, Franklin S, Chase C, Hippen A. Growth and health of holstein calves fed milk replacers supplemented with antibiotics or enteroguard 1, 2. Journal of Dairy Science. 2002;85:947-950'},{id:"B96",body:'Johnson KA, Johnson DE. Methane emissions from cattle. Journal of Animal Science. 1995;73:2483-2492'},{id:"B97",body:'Engelbrektson A, Kunin V, Wrighton KC, Zvenigorodsky N, Chen F, Ochman H, Hugenholtz P. Experimental factors affecting PCR-based estimates of microbial species richness and evenness. The ISME Journal. 2010;4:642-647'},{id:"B98",body:'Elghandour MM, Salem AZ, Castañeda JS, Camacho LM, Kholif AE, Chagoyán JC. Direct-fed microbes: A tool for improving the utilization of low quality roughages in ruminants. Journal of Integrative Agriculture. 2015;14:526-533'},{id:"B99",body:'Heinrichs A, Jones C, Heinrichs B. Effects of mannan oligosaccharide or antibiotics in neonatal diets on health and growth of dairy calves. Journal of Dairy Science. 2003;86:4064-4069'},{id:"B100",body:'Ghazanfar S. Study on the effects of dietry supplmentation of Saccharomyvces cerevisiae on performance of dairy cattle and heifers. [PhD thesis]. Islamabad. Pakistan: Quaid-e-Azam University; 2016'},{id:"B101",body:'Ghazanfar S, Qubtia M, Hassan F, Afzal M, Ahmed I, et al. Effect of indigenously isolated Saccharomyces cerevisiae probiotics on milk production, nutrient digestibility, blood chemistry and fecal microbiota in lactating dairy cows. The Journal of Animal and Plant Sciences. 2017 (Accepted)'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Shakira Ghazanfar",address:"shakira_akmal@yahoo.com",affiliation:'
Institute of Microbial Culture Collection of Pakistan, Pakistan
Department of Microbiology, Faculty of Biological Sciences, Quaid-e-Azam University, Pakistan
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Jordão",slug:"antonio-m.-jordao"}]},{id:"51863",title:"Grape Microbiome: Potential and Opportunities as a Source of Starter Cultures",slug:"grape-microbiome-potential-and-opportunities-as-a-source-of-starter-cultures",signatures:"Despina Bozoudi and Dimitris Tsaltas",authors:[{id:"180885",title:"Associate Prof.",name:"Dimitris",middleName:null,surname:"Tsaltas",fullName:"Dimitris Tsaltas",slug:"dimitris-tsaltas"}]},{id:"52041",title:"Non-Saccharomyces Yeasts: Biotechnological Role for Wine Production",slug:"non-saccharomyces-yeasts-biotechnological-role-for-wine-production",signatures:"Margarita García, Braulio Esteve-Zarzoso and Teresa Arroyo",authors:[{id:"182064",title:"Dr.",name:"Arroyo",middleName:null,surname:"Teresa",fullName:"Arroyo Teresa",slug:"arroyo-teresa"},{id:"182068",title:"Ms.",name:"García",middleName:null,surname:"Margarita",fullName:"García Margarita",slug:"garcia-margarita"},{id:"182089",title:"Dr.",name:"Esteve-Zarzoso",middleName:null,surname:"Braulio",fullName:"Esteve-Zarzoso Braulio",slug:"esteve-zarzoso-braulio"}]},{id:"52244",title:"Aroma Compounds in Wine",slug:"aroma-compounds-in-wine",signatures:"Fengmei Zhu, Bin Du and Jun Li",authors:[{id:"180555",title:"Dr.",name:"Fengmei",middleName:null,surname:"Zhu",fullName:"Fengmei Zhu",slug:"fengmei-zhu"},{id:"180943",title:"Dr.",name:"Bin",middleName:null,surname:"Du",fullName:"Bin Du",slug:"bin-du"},{id:"180945",title:"Prof.",name:"Jun",middleName:null,surname:"Li",fullName:"Jun Li",slug:"jun-li"}]},{id:"52380",title:"Influence of Yeasts in Wine Colour",slug:"influence-of-yeasts-in-wine-colour",signatures:"Morata Antonio, Loira Iris and Suárez Lepe Jose Antonio",authors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",fullName:"Antonio Morata",slug:"antonio-morata"},{id:"186423",title:"Dr.",name:"Iris",middleName:null,surname:"Loira",fullName:"Iris Loira",slug:"iris-loira"},{id:"186424",title:"Prof.",name:"Jose Antonio",middleName:null,surname:"Suárez Lepe",fullName:"Jose Antonio Suárez Lepe",slug:"jose-antonio-suarez-lepe"}]},{id:"51980",title:"New Trends in Schizosaccharomyces Use for Winemaking",slug:"new-trends-in-schizosaccharomyces-use-for-winemaking",signatures:"Ángel Benito, Fernando Calderón and Santiago Benito",authors:[{id:"180457",title:"Prof.",name:"Santiago",middleName:null,surname:"Benito",fullName:"Santiago Benito",slug:"santiago-benito"}]},{id:"52025",title:"The Use of Indigenous Yeast to Develop High-Quality Patagonian Wines",slug:"the-use-of-indigenous-yeast-to-develop-high-quality-patagonian-wines",signatures:"Silvana María Del Mónaco, Yolanda Curilen, Ramona Del Carmen\nMaturano, Sebastián Mario Ezequiel Bravo, Adriana Beatriz Simes\nand Adriana Catalina Caballero",authors:[{id:"181832",title:"Dr.",name:"Silvana María",middleName:null,surname:"Del Mónaco",fullName:"Silvana María Del Mónaco",slug:"silvana-maria-del-monaco"},{id:"181834",title:"Prof.",name:"Yolanda",middleName:null,surname:"Curilen",fullName:"Yolanda Curilen",slug:"yolanda-curilen"},{id:"181835",title:"Dr.",name:"Ramona Del Carmen",middleName:null,surname:"Maturano",fullName:"Ramona Del Carmen Maturano",slug:"ramona-del-carmen-maturano"},{id:"181837",title:"Dr.",name:"Adriana Catalina",middleName:null,surname:"Caballero",fullName:"Adriana Catalina Caballero",slug:"adriana-catalina-caballero"},{id:"182115",title:"MSc.",name:"Adriana Beatriz",middleName:null,surname:"Simes",fullName:"Adriana Beatriz Simes",slug:"adriana-beatriz-simes"},{id:"186940",title:"Mr.",name:"Sebastián Mario Ezequiel",middleName:null,surname:"Bravo",fullName:"Sebastián Mario Ezequiel Bravo",slug:"sebastian-mario-ezequiel-bravo"}]},{id:"52292",title:"Wine Lees: Traditional and Potential Innovative Techniques for their Exploitation in Winemaking",slug:"wine-lees-traditional-and-potential-innovative-techniques-for-their-exploitation-in-winemaking",signatures:"Giovanna Fia",authors:[{id:"182071",title:"Ph.D.",name:"Giovanna",middleName:null,surname:"Fia",fullName:"Giovanna Fia",slug:"giovanna-fia"}]},{id:"52255",title:"Viticultural and Biotechnological Strategies to Reduce Alcohol Content in Red Wines",slug:"viticultural-and-biotechnological-strategies-to-reduce-alcohol-content-in-red-wines",signatures:"Miguel Ángel Olego, José Manuel Álvarez-Pérez, Miguel Javier\nQuiroga, Rebeca Cobos, Mario Sánchez-García, Jesús Esteban\nMedina, Sandra González-García, Juan José Rubio Coque and José\nEnrique Garzón-Jimeno",authors:[{id:"180800",title:"Dr.",name:"Miguel Ángel",middleName:null,surname:"Olego",fullName:"Miguel Ángel Olego",slug:"miguel-angel-olego"},{id:"180814",title:"Dr.",name:"Juan José",middleName:null,surname:"Rubio Coque",fullName:"Juan José Rubio Coque",slug:"juan-jose-rubio-coque"},{id:"180816",title:"Dr.",name:"José Enrique",middleName:null,surname:"Garzón Jimeno",fullName:"José Enrique Garzón Jimeno",slug:"jose-enrique-garzon-jimeno"},{id:"187324",title:"Dr.",name:"José Manuel",middleName:null,surname:"Álvarez Pérez",fullName:"José Manuel Álvarez Pérez",slug:"jose-manuel-alvarez-perez"},{id:"187325",title:"Dr.",name:"Miguel Javier",middleName:null,surname:"Quiroga Martínez",fullName:"Miguel Javier Quiroga Martínez",slug:"miguel-javier-quiroga-martinez"},{id:"187326",title:"Dr.",name:"Rebeca",middleName:null,surname:"Cobos",fullName:"Rebeca Cobos",slug:"rebeca-cobos"},{id:"187327",title:"Mr.",name:"Mario",middleName:null,surname:"Sánchez García",fullName:"Mario Sánchez García",slug:"mario-sanchez-garcia"},{id:"187328",title:"Mr.",name:"Jesús Esteban",middleName:null,surname:"Medina",fullName:"Jesús Esteban Medina",slug:"jesus-esteban-medina"},{id:"187329",title:"Ms.",name:"Sandra",middleName:null,surname:"González García",fullName:"Sandra González García",slug:"sandra-gonzalez-garcia"}]},{id:"51885",title:"Innovations in the Use of Bentonite in Oenology: Interactions with Grape and Wine Proteins, Colloids, Polyphenols and Aroma Compounds",slug:"innovations-in-the-use-of-bentonite-in-oenology-interactions-with-grape-and-wine-proteins-colloids-p",signatures:"Milena Lambri, Donato Colangelo, Roberta Dordoni, Fabrizio\nTorchio and Dante Marco De Faveri",authors:[{id:"180897",title:"Dr.",name:"Milena",middleName:null,surname:"Lambri",fullName:"Milena Lambri",slug:"milena-lambri"},{id:"186709",title:"MSc.",name:"Donato",middleName:null,surname:"Colangelo",fullName:"Donato Colangelo",slug:"donato-colangelo"},{id:"186710",title:"Dr.",name:"Fabrizio",middleName:null,surname:"Torchio",fullName:"Fabrizio Torchio",slug:"fabrizio-torchio"},{id:"186711",title:"Dr.",name:"Roberta",middleName:null,surname:"Dordoni",fullName:"Roberta Dordoni",slug:"roberta-dordoni"},{id:"186783",title:"Prof.",name:"Dante Marco",middleName:null,surname:"De Faveri",fullName:"Dante Marco De Faveri",slug:"dante-marco-de-faveri"}]},{id:"52103",title:"The Trends and Prospects of Winemaking in Poland",slug:"the-trends-and-prospects-of-winemaking-in-poland",signatures:"Alina Kunicka-Styczyńska, Agata Czyżowska, Katarzyna Rajkowska,\nAgnieszka Wilkowska and Piotr Dziugan",authors:[{id:"181647",title:"Associate Prof.",name:"Alina",middleName:null,surname:"Kunicka-Styczyńska",fullName:"Alina Kunicka-Styczyńska",slug:"alina-kunicka-styczynska"},{id:"189006",title:"Dr.",name:"Agata",middleName:null,surname:"Czyżowska",fullName:"Agata Czyżowska",slug:"agata-czyzowska"},{id:"189007",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Rajkowska",fullName:"Katarzyna Rajkowska",slug:"katarzyna-rajkowska"},{id:"189010",title:"Dr.",name:"Agnieszka",middleName:null,surname:"Wilkowska",fullName:"Agnieszka Wilkowska",slug:"agnieszka-wilkowska"},{id:"189012",title:"Dr.",name:"Piotr",middleName:null,surname:"Dziugan",fullName:"Piotr Dziugan",slug:"piotr-dziugan"}]},{id:"52026",title:"Determination of Trace Elements in Wine by Atomic Spectroscopy and Electroanalytical Methods",slug:"determination-of-trace-elements-in-wine-by-atomic-spectroscopy-and-electroanalytical-methods",signatures:"Niina J. Ronkainen",authors:[{id:"182161",title:"Dr.",name:"Niina",middleName:"J",surname:"Ronkainen",fullName:"Niina Ronkainen",slug:"niina-ronkainen"}]},{id:"52205",title:"D-O-C Stable Isotopes, 14C Radiocarbon and Radiogenic Isotope Techniques Applied in Wine Products for Geographical Origin and Authentication",slug:"d-o-c-stable-isotopes-14c-radiocarbon-and-radiogenic-isotope-techniques-applied-in-wine-products-for",signatures:"Paraskevi Chantzi, Anastasia-Elektra Poutouki and Elissavet Dotsika",authors:[{id:"182605",title:"Dr.",name:"Elissavet",middleName:null,surname:"Dotsika",fullName:"Elissavet Dotsika",slug:"elissavet-dotsika"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"73392",title:"Pharmacogenomics: Overview, Applications, and Recent Developments",doi:"10.5772/intechopen.93737",slug:"pharmacogenomics-overview-applications-and-recent-developments",body:'
1. Pharmacogenomics: Overview
Due to variability existence among individuals against drug therapy response, it is a challenging task to predict the degree of effectiveness of a medication to a particular patient. As we know various clinical factors which are known to affect drug response, for example body size, age, sex, hepatic and renal function, and associated drug use (Table 1). Along with these clinical factors, some pharmacological factors also play a major role which includes differences in metabolism, drug distribution and drug directed proteins [2, 3]. Recently, major causes of interindividual differences are shown by variations in genes encoding cytochrome P450 (CYP) and other metabolizing enzymes in plasma concentrations of some drugs [4, 5].
Factors
Effects
a. Genetic factors
Drug-metabolizing enzymes
Drug metabolism (pharmacokinetics)
Therapeutic targets
Drug efficacy (pharmacodynamics)
Targets of ADRs
Drug toxicity
Drug transporters
Drug disposition
b. Environmental factors
Environmental chemicals, alcohol drinking, combined drugs effect, and dietary substances
Genome-wide association studies in pharmacogenomics [1].
Pharmacogenetics and pharmacogenomics can be used interchangeably. Though, Pharmacogenomics refers to the whole range of genes that are related to the determination of drug efficacy and safety whereas pharmacogenetics means monogenetic variants which alter the drug response [6, 7]. Pharmacogenomics is defined as study of genes and how they affect an individual response to the administered drugs. Pharmacogenomics is emerging new branch with combination of both pharmacology (branch of science which deals with study of drugs) as well as genomics (the branch of science which deals with study of genes) for development of effective doses and safe medications tailored according an individual patient genetic makeup (Figure 1) [8, 9].
Figure 1.
Development of pharmacogenomics and pharmacogenetics.
Basically, the concept for pharmacogenetics was left unknown for more than 50 years. This study underlined to the molecular mechanisms in account for their variation in responses to drug due to inherited characters and in drug development process. Pharmacogenomics applications can be employed in the improvement of discovery of new entities and its development with two possible ways: target the new drug targets or development of new entity to overcome drug resistance, and another way is to optimize the pharmacokinetics and metabolism of drug for reduction of the drug level variations [10]. In fact, personalized drug therapy or individualized drug therapy is not an easy task. It needs many folds as there may be a lack of information regarding drug action, genomic elements of important disease pathogenesis, especially for complex diseases. Also, large scale clinical studies are sometimes becoming a big challenge for the researchers [11]. The correlation of pharmacogenomics and cancer would expand the specific anticancer drugs with better chemotherapeutic outcomes [12, 13, 14, 15]. There are prominent examples with recent clinical and pharmaceutical restrains where the molecular based mechanisms are involved in various drug responses were observed among the patients and diagnosed with the similar diseases [16, 17]. Moreover, various polymorphisms existence at genetic levels in genes found to have association with alteration in responses of drug and rate of ADRs in humans (Table 2) [18].
Polymorphic gene
Drug
Effect
CYP2C9
Phenytoin
Toxicity
Warfarin
Bleeding risk
Glipizide
Hypoglycaemia
TPMT
Anticancer drugs like 6-thiopurine, 6-Mercaptopurine, azathioprine
Toxicity
Human leukocyte antigens (HLA)
Abacavir
Related to hypersensitivity
N-acetyltransferase (NATs)
Sulphonamides, hydralazine, Isoniazid
Toxicity, hypersensitivity
UDP-glucuronosyltransferase 1A1 (UGT1A1)
Irinotecan
Toxicity
CYP2D6
Codeine
Toxicity
Fluoxetine
Toxicity
MDRI
Antiepileptic drugs
Drug response
Table 2.
Genes with altered drug response.
Finally, pharmacogenomics-based development of drug and its regulation will open the doors for new as well as targeted drug development for promoting safe, effective, and cost-effective drug therapy for individual. The theoretical origin for pharmacogenomics is outlined by Sir Archibald Garrod’s in book entitled as “1939 Inborn Factors of Disease” [19].
Pharmacogenetics is the study of how an individual person’s genes respond to a drug. This branch is associated with genomics is genetic level studies with functional studies and pharmacology (includes pharmacokinetics and pharmacodynamics). All these branches together aid in the development of safe, and effective medications along with doses which are probably tailored to an individual persona genetic makeup [20, 21, 22, 23, 24]. Pharmacogenetics is indicated as major clinically proven application in terms of advancement in human genomic science. This potentiates a revolution in drug therapy. As a result, diseases which range from depression to viral infection and from childhood leukemia to hypertension are treated or controlled for enhancing the quality of life of patient. Most medicines at present are available as “one medication fits all” but they sometimes were not capable to work same to everyone. So, it is difficult to envisage who will have benefit result and who will have negative side effects. Also, the knowledge which scientist have acquired due to extensive work on Human Genome Project and are learning about inherited variations of genes and there effect on body’s response to medications. Conditions in which responses of an individual to certain drugs include Stevens-Johnson syndrome or epidermal toxic necrolysis, clopidogrel resistance, malignant hyperthermia, warfarin sensitivity and its resistance and thiopurine S-methyltransferase deficiency [25].
2. Application
Many common diseases having high morbidity as well as mortality rates have now known with well-established genetic components. The degree of role of genetics has been predicted for diseases like obesity and diabetes according to their sibling analysis [26, 27]. In the same way, some rare gene mutations can provide a vision into the more complex biological processes [28]. For instance, when the subject possesses extreme levels of HDL in their blood, one can easily demonstrated the influence of CETP (cholesteryl ester transfer protein) on patients HDL levels [29, 30, 31]. In another case, a person having deactivating mutations due to the Janus kinase 3 (JAK 3) gene shows severe combination of immune-deficient syndrome, as sometimes inhibition of JAK3 was expected to affect the human immune suppression [32, 33]. Hence, this led to a new investigation on drugs having CETP inhibition and JAK3 inhibition with the help of pharmacogenetics [34]. Also, with the advent of pharmacogenomics, the path of relationships between disease state and human genes has now established which led to the suitable selection of therapeutic targets.
Nowadays, many academic institutions and Pharmaceutical companies are moving toward the investigation on the relationship between disease phenotypes and genetic variations to better categorize diseases [35, 36]. Although the collection of medical phenotypes having linkages with samples of DNA provides a prominent opportunity for examine the genetic variation which are present in patients. Investigation of genetic variation can be done by collection of DNA of particular patient. This is characterized in a study where DNA from a person involves in trails of lipid lowering demonstrated a swift connection between phenotypic novel lipase gene family and for HDL levels. As per literature reports, above mentioned studies are based on a sound hypothesis which is linked to candidate’s biological gene selection. Now it is easy to cross-examine the genome selection which is solely depends on phenotypic criteria [10, 37]. These stages have now substituted around 300,000 SNPs across the genome, by exploiting only few haplotype-defining SNPs. Perlegen sciences have developed newly genotyping technologies which has with a capability of genotyping mass hundreds or thousands of markers with the help of high-density based oligonucleotide arrays linked with restriction enzyme-based genomic reduction. However, as these technologies advances, still exact number of haplotype-defining SNPs is uncertain. Some findings are recently reported relation to assess polymorphisms across selected gene regions recommends that, it is necessary to reach an r2 of >0.8% in order to detect more than 80% of all haplotypes. Due to HapMap project progression with defined LD patterns linkage, scientist working on genes will thorough assess to the degree of LD in a represented regions or selected regions. This will enable to explore more around selection of SNP regardless design of study [38, 39]. As genome approach does not depend upon selection of candidate genes, so understanding on complex diseases such as psychiatric or cardiovascular diseases will become more efficient. Some researchers believed that the new horizons on LD coverage about insights of human genome and SNP density will show the perception of a substantial genomic portion areas and its relation with interest of phenotype [40, 41]. To assess the Perlegen Sciences chip-based array-based platform and to justify the haplotype tagging approach for the identification of genetic associations, 7283 SNPs connecting 17.1 mega bases (Mb) of DNA were genotyped for detecting linkages with HDL levels. Further, SNPs were connected with 50 CETP haploblock gene were found out as the most valuable association in dataset. The companies like Perlegen and project like Hap Map project recently declared their purpose to provide it SNPs markers into public provinces to further advent to basis for such kind of experiments which help in the scientific community [42, 43].
Pharmacogenetics significantly expands the therapy outcomes and drug uses. Medications may prescribe in low dose under strict monitoring to patients which shows genetically predisposed to their adverse events. This would probably helpful for drugs having narrow therapeutic index such as warfarin may be started gradually in patients having VKORC1 genotype linked with improved warfarin sensitivity. With the help of pharmacogenetics, it is now possible to reduce the number of subjects to conduct any experiment and chances of error may be eliminated for many diseases [44, 45].
On the contrary, clinicians may be able to minimize possible adverse effects with the aid of genetic information for matching suitable drug to suitable patient at an appropriate dose. For instances, traditional approach to the management of hypertension involves the trial of numerous anti-hypertensive drugs till the desired blood pressure achieved with adequate drug tolerability. In this case, few initial drugs/agents fail to produce lower blood pressure or shown intolerable adverse effects. This way of selection of drugs took long time which ultimately suffered by patients. On the contrary, Pharmacogenetics, based on the patients’ DNA, offers the greatest response with the best tolerability of the drug. Based on genetic regulator of cellular functions, pharmacogenetics may be able to produce new drugs with less adverse effects. For example, chromosome translocation and its derived enzymes are responsible for causing life-threatening chronic myeloid leukemia (CML) which led to accelerate FDA approval of inhibitor of translocation-created enzyme Imatinib [46]. In the end, this core subject improves the quality and cut-down the total costs of healthcare by minimizing the number of adverse reaction and reduce treatment failures gives rise to the discovery of new genetic targets for disease management [47, 48, 49].
3. Case studies
3.1 Thiopurine therapy and TPMT (thiopurine methyltransferase) testing
Thiopurine are the categories of drugs that are used to conquer the normal activity of the body’s immune system. In short, these are called antimetabolites chiefly used as an antiproliferative as well as immunosuppressants such as mercaptopurine and azathioprine. 6-mercaptopurine daily administered for 3–4 years for treating childhood leukemia, while azathioprine which is a prodrug of 6-mercaptopurine prescribed for treating inflammatory bowel disease (also known as Crohn’s disease) [50]. TPMT methylates thiopurine compounds. S-adenosyl-L-methionine acts as methyl donor and converts it into S-adenosyl-L-homocysteine [51, 52]. So, TPMT metabolizes various thiopurine based drugs with mechanism of S-adenosyl-L-methionine while S-methyl acting as donor, while S-adenosyl-L-homocysteine acting as a derivative. Genetic polymorphism which affects basically enzymatic activity has association with variations in toxicity and sensitivity within individuals due to such drugs. Nearby 1/300 individual is lacking for this enzyme. TPMT has not recognized to have any phenotype in the absence of encounter drug. TPMT is now enlists by FDA as a pharmacogenomic biomarker for various adverse drug reactions related to cisplatin such as cisplatin-induced ototoxicity in teenagers [47, 53, 54, 55].
Patients having identical alleles at equivalent chromosomal loci accumulate unnecessary thioguanine nucleotides levels (up to 10-fold higher related with wild types) and treatment with standard dosages of drug and leading to a hematopoietic toxicity (pancytopenia and myelosuppression) which is life-threatening condition [56, 57].
In more concise way, patients having heterozygous gene variations are also at high risk in terms of toxicity and dosage reductions is prior in these cases up to their tolerate therapy. According to pharmacoeconomic studies, the determination of the TPMT genotype is cost-effective and it must be checked prior to the start of therapy. According to a review of the literature, it was found that TPMT testing with clinical performances for myelosuppression was estimated with specificity of 89%, sensitivity of 32%, 9% PPV and NPV of 97% (Table 3). The low estimated value represents low incidence of severity in myelosuppression especially in those patients who are carrier of not less than one defective allele. Researchers have estimated the net cost for avoidance of serious events of myelosuppression. Out of 1000 patients receiving azathioprine, only 3.2% (equivalent to 32 cases) have founded with severe leukopenia and TPMT screening avoided as third of those trials [50, 58].
Clinical performances
(%)
Percent responders
40.0
Sensitivity
75.0
Specificity
66.7
Frequency mutation
50.0
Positive predictive value (PPV)
60.0
Negative predictive value (PPV)
80.0
Table 3.
Clinical performances of the test.
Iorio and co-workers have analyzed drug responses on various human cancer cell lines. The mapping was done for around 11K tumors obtained from different 29 different human tissues as per Cancer of Genome Atlas (TCGA) enlisted from 1000 cancer cell lines as per Genomics of Drug Sensitivity in Cancer resource. In another event, TCGA patient gene expression was studied for drug response. In this, more than 140 gene drug interactions were studied with specific somatic biomarkers [59, 60, 61].
3.2 Abacavir therapy and HLA testing
Abacavir which is HIV-1 nucleoside with reverse transcriptase inhibition is employed for management of HIV/AIDS. It is well tolerated but sometimes shows common to more severe side-effects which include lactic acidosis, hypersensitivity [62]. In some studies, it was observed that a genetic testing/marker can help in predicting whether a HIV-infected patient is at high risk of abacavir induced severe hypersensitivity reactions (approx. 5% of patients) [63, 64]. This hypersensitivity reaction accompanies with lethal gastrointestinal symptoms, rashes, and fever. This reaction is life threatening, particularly if drug is restarted and discontinued. One study has shown about an occurrence of human leukocyte antigen (HLA)B05701 is main cause of hypersensitivity [45, 65]. Based on the Australian cohort, patients were 114 times more hypersensitivity due to HLA-B5701 allele reaction, whereas in an industry-sponsored study revealed that patients with the HLA-B5701 allele was associated with 24 times more likely to experience of hypersensitivity reaction [45]. Thus, one way to solve this issue is genetic testing which integrates pharmacogenetics into the clinical practice. The distribution of HLA-B5701 allele can be detected in many worldwide populations (Table 4).
Population group
HLA-B5701 carrier frequency range (%)
Asian
00–6.5
Southwest Asian
4–19.5
Middle Eastern
0.5–6.2
African
0.0–3.5
European
1.5–10.5
Mexican
0.0–4.2
South American
1.2–3.2
Table 4.
Allele frequency of HLA-B5701 allele in various population groups.
3.3 Statin therapy and polymorphic angiotensin-converting enzyme
Statins (HMGCoA) reductase inhibitors most often used in management of hypercholesterolemia condition accompanying with elevation in risk to coronary heart disease [66, 67]. Due to increased number of cases of hypercholesterolemia along with volume of statins related prescriptions in US, it creates a significant interest in optimization of costs related to these therapies [31]. Recent investigations have told that polymorphism in I/D angiotensin converting enzyme (ACE) has correlation with risk of heart related syndromes in men when treated with statins [68, 69, 70]. Next 2 years of statin medication, in which males who are having DD genotype (equivalent to 27% of patients) shown to have no effect on the risk of coronary heart disease (with relative risk factor of 1.34), in comparison to males with ID (equivalent to 21% of patients) present a marked decreased in risk of coronary cardiovascular disease (with relative risk rate of 0.87), II genotype (equivalent to 22% of patients) having relative risk of 0.23, thus concluding that patients bearing DD genotype did not take advantages from statin treatment. Also, testing of I/D genotype might results in cost effective as few patients presents the I/I or I/D genotype [70].
3.4 Muscle relaxant succinylcholine and antitubercular drug, INH
These two conventional illustrations of pharmacogenetics involve the genetic variation along with enzymatic metabolism (enzymatic hydrolysis and acetylation). Both act as a monogenic trait and involved PK variations because of inheritance differences [71, 72]. It was observed that some patients with succinylcholine treatment experienced a serious and lethal adverse event i.e. prolonged muscle paralysis which is due to inherited “atypical” butyryl cholinesterase enzyme (BCHE). Later, it was established that BCHE allele which encodes the most usual atypical form of enzyme comprised with a nonsynonymous coding i.e. single nucleotide polymorphism (nSNP), G209 > A, results in Asp70 > Gly change in encoded amino acid which altered active sites of enzyme [73, 74]. But atypical BCHE has less ability to catalyze the succinylcholine hydrolysis and could resist to inhibition due to dibucaine compound [37, 75].
Tuberculosis is the most problematic disease of both developing as well as under-developed nations. The conformity to patients with tuberculosis is due to common lethal adverse reactions and supposed to have important aspect providing high prevalence [76, 77]. Many investigations showed that the polymorphisms of N-acetyl transferase 2 (NAT-2), CYP2E1 as well as glutathione S transferase (GST-1) would be able to influence concentration of liver toxic isoniazid metabolites in plasma. Some polymorphic genes contribute in the INH induced hepatotoxicity by altering the anti-oxidant enzyme expression, these gene polymorphisms include glucuronosyltransferase (UGT), basic region of leucine zipper factor family (CNC) homolo (BACH), human leukocyte antigen (HLA), nitric oxide synthase (NOS) and Maf basic leucine zipper protein (MAFK). Till date the above mentioned studies encounter with many limitations [77, 78, 79].
3.5 Warfarin
Warfarin is a medication that is commonly used as an anticoagulant which means blood thinner. It aids in treating blood clots such as pulmonary embolism and deep vein thrombosis, and to prevent heart diseases associated with clotting. It has very narrow therapeutic index [80, 81]. However, warfarin therapy may result in complicated adverse reactions including both coagulation and hemorrhage. The racemic mixture of warfarin, S-form is 3–5 times more potent in comparison to R-form of an anticoagulant, and easily gets metabolized due to genetically polymorphic CYP450 isoform i.e. CYP2C9 [82]. CYP2C9 exists in two common polymorphic form, Arg144 > Cys (CYP2C9*2) as well as Ile358 > Leu (CYP2C9*3) modifications in coded sequence of amino acid, with nearly 12 and 5%, respectively. These forms vary between 8 and 10% in Caucasians, with minor occurrence in subject from Southeast Asia. A report in 1999, which confirms patients with one or two common CYP2C9 variant alleles, requires a “low” warfarin dose. These subjects had a risen risk of hemorrhage during warfarin therapy. In 2004, the gene encoded targeting VKORC1 (vitamin K epoxide reductase complex 1) was cloned. In a study, it was found that patients with VKORC1 type of haplotypes requires low dose, the average warfarin maintenance dose was nearly half for subjects with haplotypes having high dose maintenance. In this study, the grouping of both VKORC1 haplotyping as well as genotyping for CYP2C9 described around 25% of dose variance in warfarin. Other studies reported similar results in 2005. The Pharmacogenetics Knowledge Base (PharmGKB), in which data base is reinforced by the National Institutes of Health (NIH) along with part of the NIH Pharmacogenetics Research Network (PGRN), originated an association for consolidation of warfarin pharmacogenetic data throughout the world [83, 84]. In this evaluation of variation in genetic drug target as well as drug metabolism if and only if when VKORC1 and CYP2C9 haplotypes were determined. The figure demonstrates a schematic illustration of both pharmacokinetic (CYP2C9-dependent) as well as pharmacodynamic (VKORC1-dependent) pharmacogenomic aspects that effects final dose of warfarin (Figure 2).
Figure 2.
Warfarin pharmacogenomics.
It is important to know that by identifying the individual genetic properties, we can improve the dosing of warfarin. In general, VKORC1 haplotypes have three-fold greater effect on an individual’s warfarin dose than CYP2C9. Both can play a vital role in the potential for estimating the therapeutic warfarin dose. In August 2007, FDA approved a change in labeling of warfarin package stating, “lower starting doses should be considered for patients with some genetic alterations in VKORC1 and CYP2C9 enzymes” [80].
4. Outlook
These cases prove that patient care could be improved effectively by pharmacogenetic based approaches. Although, the allelic occurrences of the gene alterations must be visibly defined in the subjects studied must be well established. Out of above-mentioned cases, no one is absolute, so it is better to perform the sensitivity analyses as well as to regulate the robustness of conclusion with variation in probabilities [85, 86]. Move onward, it is utmost important for maintaining the possible cost-effectiveness of few recently published pharmacogenetic associated reports, for instance, vitamin K epoxide reductase gene variants envisage the warfarin response [87, 88, 89]. Lastly, it will be significant to collect pharmacoeconomic and pharmacogenetic statistics together during industry-funded clinical trials for bringing cost effective theragnostic in a sensible manner [90, 91].
5. Conclusion
Individualized therapeutics or tailor-made therapy is one of the major goals of pharmacogenomics. In relation to inheritance other factors also contribute to individual therapeutics due to variation in response to administration of drug. Recently many developments in the field of pharmacology and genomics have made possible for physicians to achieve individualization of therapeutics. These recent developments create possibility of thorough basis of particular drug for particular patient with motive of tailor-made therapy. Futuristic development in field of pharmacogenomics has paved the way to new emerging fields of pharmacoproteomic, pharmacotranscriptomics, and pharmacometabolomic. These new branches of science make it possible to achieve the concept of treat each patient as unique, complex, fascinating individual. At the end doubts about achieving individualized therapeutics with the help of this integrated system is still a dream in 21st century era.
Acknowledgments
The NIPER-R communication number for this manuscript is NIPER-R/Communication/156.
Conflict of interest
The authors declare no conflict of interest among themselves.
\n',keywords:"pharmacogenomics, genomics, proteomics, personalized medicines, tailored drugs",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73392.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73392.xml",downloadPdfUrl:"/chapter/pdf-download/73392",previewPdfUrl:"/chapter/pdf-preview/73392",totalDownloads:116,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 22nd 2020",dateReviewed:"August 25th 2020",datePrePublished:"October 12th 2020",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Pharmacogenomics is defined as the study of genes and how an individual response is affected due to drugs. Pharmacogenomics is an emerging new branch with combination of both pharmacology (the branch of science that deals with study of drugs) as well as genomics (the branch of science that deals with study of genes) for development of effective doses and safe medications tailored according an individual patient genetic makeup. Human Genome Project is one of the crucial projects in which researchers are developing and learning relation in genes and its effect on the body’s response to medications. Difference in genetic makeup provides difference in effectiveness of medication and in future to predict effectiveness of medication for an individual and to study existence of adverse drug reactions. Besides advancement in the field of science and technology till date pharmacogenomics hangs in infancy. There is limited use of pharmacogenomics, but still, novel approaches are under clinical trials. In near future, pharmacogenomics will enable development of tailor-made therapeutics for treating widespread health problems like neurodegenerative, cardiovascular disorders, HIV, cancer, asthma, etc.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73392",risUrl:"/chapter/ris/73392",signatures:"Rahul Shukla",book:{id:"9831",title:"Drug Design - Novel Advances in the Omics Field and Applications",subtitle:null,fullTitle:"Drug Design - Novel Advances in the Omics Field and Applications",slug:null,publishedDate:null,bookSignature:"Dr. Arli Aditya Parikesit",coverURL:"https://cdn.intechopen.com/books/images_new/9831.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Pharmacogenomics: Overview",level:"1"},{id:"sec_2",title:"2. Application",level:"1"},{id:"sec_3",title:"3. Case studies",level:"1"},{id:"sec_3_2",title:"3.1 Thiopurine therapy and TPMT (thiopurine methyltransferase) testing",level:"2"},{id:"sec_4_2",title:"3.2 Abacavir therapy and HLA testing",level:"2"},{id:"sec_5_2",title:"3.3 Statin therapy and polymorphic angiotensin-converting enzyme",level:"2"},{id:"sec_6_2",title:"3.4 Muscle relaxant succinylcholine and antitubercular drug, INH",level:"2"},{id:"sec_7_2",title:"3.5 Warfarin",level:"2"},{id:"sec_9",title:"4. Outlook",level:"1"},{id:"sec_10",title:"5. Conclusion",level:"1"},{id:"sec_11",title:"Acknowledgments",level:"1"},{id:"sec_14",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Daly AK. Genome-wide association studies in pharmacogenomics. Nature Reviews. Genetics. 2010;11(4):241-246'},{id:"B2",body:'Caldwell MD, Berg RL, Zhang KQ, Glurich I, Schmelzer JR, Yale SH, et al. 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Interindividual variability in TPMT enzyme activity: 10 years of experience with thiopurine pharmacogenetics and therapeutic drug monitoring. Pharmacogenomics. 2014;15(6):745-757'},{id:"B54",body:'Lennard L. Implementation of TPMT testing. British Journal of Clinical Pharmacology. 2014;77(4):704-714'},{id:"B55",body:'Ford LT, Berg JD. Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. Journal of Clinical Pathology. 2010;63(4):288-295'},{id:"B56",body:'Moran GW, Dubeau MF, Kaplan GG, Yang H, Eksteen B, Ghosh S, et al. Clinical predictors of thiopurine-related adverse events in Crohn’s disease. World Journal of Gastroenterology: WJG. 2015;21(25):7795'},{id:"B57",body:'Roberts RL, Barclay ML. Current relevance of pharmacogenetics in immunomodulation treatment for Crohn’s disease. Journal of Gastroenterology and Hepatology. 2012;27(10):1546-1554'},{id:"B58",body:'Wang L, Weinshilboum R. 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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
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Open Access Funding
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Live Performance Metrics to track readership and the impact of your chapter
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Proven world leader in Open Access book publishing with over 10 years experience
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+146,150 citations in Web of Science databases
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Currently strongest OA platform with over 130 million downloads
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