1. Probiotics and Prebiotics: Current Status and Future Trends

Koen Venema and Ana Paula do Carmo

Over the past several decades the research into the health benefits of probiotics and prebiotics has rocketed sky high. There are several new applications and diseases and disorders for these healthy dietary components that were previously unthinkable. However, the efficacy has not been scientifically substantiated for all these applications yet, and care needs to be taken that pro- and prebiotics are not considered as a cure for everything. For starters, probiotic effects are strain dependent, and hence not all strains are beneficial for all disorders. In fact, some strains may be detrimental when given to certain patients, and it may aggravate the problems that these patients have. Similarly, prebiotics are not identical, and will stimulate different microorganisms in different individuals, in some case leading to worsening of the disease. Moreover, dose-dependency has rarely been studied and in the case of probiotics, culture conditions may affect their efficacy as well. In addition, although numerous positive results have been obtained with several well-studied probiotic strains, the mechanism of action usually is still completely unclear, let alone what the molecular molecule is that is responsible for the benefit. So, despite several decades of intense research there is still much to be discovered.

2. Functional Aspects of Prebiotics and the Impact on Human Health

Vicky De Preter and Kristin Verbeke

Due to the recent developments in analytical techniques to analyse the composition of complex microbial ecosystems, our understanding of the intestinal microbiota has tremendously increased. Several disorders have been associated with an altered composition of the gut bacteria. As a consequence, the microbiota is increasingly recognized as a therapeutic target to improve health. Besides having a trophic and protective function, the microbiota is a metabolically very active ecosystem. Amongst the wide variety of metabolites produced, short chain fatty acids (SCFA) constitute the most relevant compounds in relation to health. As far as we know to date, administration of prebiotics selectively modifies the composition of the intestinal microbiota through several mechanisms and favours the saccharolytic fermentation resulting in increased SCFA production. These SCFA play a pivotal role in the health benefits associated with prebiotic intake as they acidify the colonic lumen, which influences metabolic pathways and inhibits pathogens, and act as signaling molecules on specific receptors. In the future, more detailed information on the exact role of each individual SCFA and on the proportion of the SCFA produced from different prebiotic substrates will be essential to further exploit the benefits of prebiotic use.

3. Lactobacilli as Probiotics: Discovering New Functional Aspects and Target Sites

Koen Venema and Marjolein Meijerink

Probiotic lactobacilli have been in use for several decades now. Still, we hardly know the molecular mechanisms underlying the probiotic effect. Two strains, L. rhamnosus GG and L. plantarum WCFS1 have been studied in great detail, and mutants of these strains have greatly aided in our understanding of the interaction with the host. However, several surprising results were obtained as well, and leave more questions than answers. The first part of this chapter lists the recent advances in the molecular understanding of interaction of probiotic lactobacilli with the host. Especially surface molecules are thought to play a crucial role in this interaction. In the second half of the chapter we briefly highlight some of the newest applications. Although there have not been a lot of studies with these novel approaches, the initial results are promising and require further research, not only to confirm the results found, but also to deduce the mode of action of these probiotics.

4. Bifidobacteria: Regulators of Intestinal Homeostasis

Thomas D. Leser, Caroline T. Gottlieb and Eric Johansen

Bifidobacteria are natural inhabitants of the gastrointestinal tract possessing genetic adaptations that enable colonization of this harsh and complex habitat. Due to their recognized benefits to human health bifidobacteria are used as probiotics; however industrial-scale production of bifidobacteria is a challenge. Bifidobacteria interact with key elements of intestinal functioning and contribute to maintaining homeostasis. Recent scientific progress has demonstrated that bifidobacteria, through strain-dependent interactions with the host may reduce mucosal antigen load, improve the intestinal barrier, and induce regulation of local and systemic immune responses. Continued research on Bifidobacterium-host interactions is expected to bring knowledge on the mechanisms involved in these health effects, and to support the identification of even more efficacious strains that will increase the variety of commercially available products.

5. Propionibacteria also have Probiotic Potential

Gabriela Zárate and Adriana Perez Chaia

Propionibacteria were first described by the end of the nineteenth century and named some years later by Orla-Jensen (1909) who proposed the genus Propionibacterium for referring to bacteria that produce propionic acid as their main fermentation end-product. Based on habitat of origin, they are conventionally divided into "classical or dairy" and "cutaneous" microorganisms which mainly inhabit dairy/silage environments and the skin/intestine of human and animals, respectively. Historically, the economic relevance of Propionibacterium has been related to the industrial application of classical species as dairy starters for cheeses manufacture and as biological producers of propionic acid. However, propionibacteria also display probiotic potential. Over the last two decades, the ability of these microorganisms to improve the health of humans and animals by being used as dietary microbial adjuncts has been extensively demonstrated. Both in vitro and in vivo studies revealed that propionibacteria are able to modulate in a favorable way gut physiology, microbiota composition and immunity. Much of these health benefits could be related to the ability of propionibacteria to remain in high numbers in the gastrointestinal tract by surviving the adverse environmental conditions and adhering to the intestinal mucosa. In addition, other promising properties like the production of nutraceuticals and relevant biomolecules such as vitamins B and K, conjugated linoleic acid (CLA), exopolysaccharides (EPS), trehalose, bifidogenic factors, bacteriocins, etc have been reported. In recent years, the availability of genome sequences of different propionibacteria species have allowed to deep insight into the metabolism and physiology of these microorganisms and became a useful tool for selecting appropriate strains for technological, functional or probiotic applications. In the present chapter, we review exhaustively the evidences that support the potential of propionibacteria to be used as probiotic supplements for human and animal nutrition. Besides the positive results on health obtained by us and others, the hardiness and adaptability of propionibacteria to both technological and physiological stresses encourage their usage for designing new functional foods.

6. Non-LAB Probiotics: Spore Formers

Loredana Baccigalupi, Ezio Ricca and Emilia Ghelardi

A growing body of evidence suggests that probiotics can be efficiently used to treat/prevent some illnesses, from gastro-intestinal or urogenital disorders to allergies, cardiovascular and autoimmune diseases and even to prevent the onset of certain cancers. Although Lactic Acid Bacteria (LAB) and bifidobacteria are the most common microbes used in probiotic preparations, yeasts and other bacteria are also widely used. This chapter focus on the use of bacterial spore formers as probiotics. Spore formers are a group of bacteria able to form an endospore (spore), an exceptionally resistant cell that contains all of the necessary genetic information needed to regenerate a new vegetative cell. Bacterial spores have been commercialized as probiotics for more than 50 years and are now extensively used in humans for the treatment of intestinal disorders and as dietary supplements, in animals as growth promoters and competitive exclusion agents and in aquaculture for enhancing the growth and disease-resistance of cultured fish and shrimps. This chapter will first describe the group of spore-forming bacteria, the sporulation process, the structure of the spore and its interactions with human intestinal and immune cells and then summarize the use of some spore former species as probiotics for human and animal use.

7. Mechanisms of Action of Probiotic Yeasts

Flaviano dos Santos Martins and Jacques Robert Nicoli

Some yeasts such as Saccharomyces boulardii 17 and Saccharomyces cerevisiae UFMG 905 can be used as probiotics to prevent or treat various infectious and inflammatory diseases. Similar to bacterial probiotics, beneficial effects of these yeasts are the results of simultaneous action of various mechanisms such as modulation of some aspects of local and systemic immune responses, trapping of bacterial toxin or pathogenic bacterial cells on yeast surface, and maintenance of intestinal epithelium integrity. Acting together, these mechanisms seem to be responsible for a reduction of inflammatory process, intestinal permeability and bacterial translocation observed during infectious and inflammatory diseases.

8. Yeasts as Probiotics: Established in Animals, but What About Man?

Gunnard K. Jacobson

Yeasts are single-celled fungi that have been associated with human activity for thousands of years. Yeast strains of Saccharomyces cerevisiae have always been a good, and traditional, source of animal and human nutrition because of their B vitamin content. The use of inactive yeasts, live yeasts, and live yeast products such as "yeast culture" is widespread in animal husbandry. The traditional use of yeast by man has been primarily in food modification (leavening and alcoholic fermentation), but also medicinally, and as a nutritional supplement. Only within the last century have the probiotic properties of some yeast strains been recognized: increased milk yields in dairy cattle and ameliorating diarrheal diseases in man, for example. Some properties may be generic, e.g., oxygen scavenging in the rumen; but other properties are not shared by all strains of Sacch. cerevisiae and the explanations for this fact are under intense scientific scrutiny. The probiotic attributes of the boulardii subgroup of strains within Sacch. cerevisiae have been attributed to effects on enteric pathogens, intestinal barrier function integrity, anti-inflammatory effects, immune stimulation, and trophic effects on the intestinal mucosa. Current research is identifying new yeast probiotics outside of the Sacch. cerevisiae ssp. boulardii cluster.

9. Escherichia coli: More Than A Pathogen?

Maïwenn Olier

Escherichia coli is well recognized by the wider public for its ability to cause from self-limiting to life-threatening intestinal and extra-intestinal illnesses. E. coli infections remain actually, and primarily, a global public health concern both in developed and developing countries, explaining, at first glance and understandably, the negative connotation associated with this bacterium. Consequently, E. coli employment for therapeutic purpose may be considered as an aberrant concept. We ought however to keep in mind that E. coli is not only a pathogen. Originally isolated from neonatal stools, characterized and named Bacterium coli commune by Theodor Escherich (1884, reprinted in (Escherich, 1988)), E. coli represents the predominant facultative anaerobic resident of our gut microbiota, where it behaves, at first sight, commensally. Nevertheless, clinical and preclinical beneficial effects of certain E. coli strains on the host, i.e. the probiotic E. coli strains, have also been demonstrated and they are reviewed herein. This chapter summarizes current advances in understanding geno- and phenotypic features that allow to discern the pathogen from the commensal or the probiotic E. coli. Findings in this field highlighted how complex it sometimes is to establish a clear border between probiotic and pathogenic features within E. coli populations. Consequently, ready-made guidelines for the use of probiotic E. coli strains by practicing physicians are still lacking.

10. The Paradoxical Role of Enterococcus Species in Foods

Luís Augusto Nero, Svetoslav Dimitrov Todorov and Luana Martins Peri

Enterococcus species present a diversity of genetic and phenotypic features, allowing them to present a high capacity to survive and grow at different conditions, explaining its constant presence in food production and processing environments and in end products. These microorganisms are able to produce a wide variety of virulence factors, highlighting their relevance as safety indicators in foods; however, they are also able to produce bacteriocins, called enterocins, and to promote specific modifications in food during fermentation. Enterococci are present in a variety of ripened cheeses, especially from the Mediterranean region, being responsible for specific aromas and flavors that determine the characteristics of these artisanal foods. Also, many Enterococcus species were characterized due to their probiotic potential, being included in commercial products to be consumed by humans and animals, aiming the promotion of health and well-being. Despite being known for possessing virulence genes, many studies demonstrated the absence of expression of such genes, especially isolates obtained from food systems, leading to studies that investigate their real relevance as pathogenic microorganisms. So, this paradoxical role of enterococci in foods must be properly discussed by food microbiologists, which is the focus of this chapter.

11. Use of recLABs: Good Bugs to Deliver Molecules of Health Interest. From Mouse To Man

Jean-Marc Chatel, Natalia Breyner, Debora Rama, Vasco Azevedo, Anderson Myioshi and Philippe Langella

Lactic acid bacteria (LAB) constitute a heterogeneous group of Gram-positive bacteria widely used in the food industry because of their generally regarded as safe (GRAS) status. In this regard, LAB have been widely investigated and used as live vehicles for the production and delivery of heterologous proteins or cDNA of vaccinal, medical or technological interest because of its ease for protein secretion and purification. Here, we review the expression of heterologous protein and the various delivery systems developed to target heterologous proteins to specific cell locations (cytoplasm, extracellular medium or cell wall), as well as the more recent research on LAB as DNA delivery vehicles and finale with the challenges and future trends to improve the existing strategies and develop new ones.

12. The Indigenous Microbiota and its Potential to Exhibit Probiotic Properties

Sylvie Miquel, Rebeca Martin, Muriel Thomas, Luis G. Bermudez-Humaran and Philippe Langella

Humans harbour a different microbiota depending on the tissue considered. Most of the microorganisms are contained in the gastro-intestinal tract (GIT) and this gut microbiota represents approximately 1014 cells that correspond to the highest bacterial density for any ecosystem. Our microbiota represents a huge diversity in term of species and functions. A healthy gut microbiota is composed of a well-balanced community of three permanent residents termed symbionts (with beneficial effects), commensals (no effect), and pathobionts (potentially induce pathologies under certain situations), but no pathogens. The term dysbiosis (microbial imbalance) has been related to many different kinds of pathologies although it is not clear whether the imbalance of such a microbiota is a cause or a consequence of the illness. Nowadays, the challenge of linking microbiota to human health and disease is being tackled by different research teams around the world with the aim to investigate the implication of potential beneficial bacteria that could be decreased in the studied microbiota of patients. From this perspective, it could be interesting to use them as potential probiotics to try to resolve dysbioses.

13. Improving the Digestive Tract Robustness of Probiotic Lactobacilli

Hermien van Bokhorst-van de Veen, Peter A. Bron and Michiel Kleerebezem

This chapter describes stress responses of probiotic lactobacilli, in relation to gastrointestinal (GI-)tract robustness. An overview is given of some newly developed tools to understand and improve stress responses of the model probiotic L. plantarum WCFS1 in relation to its GI persistence. These include a relative simple GI-tract assay and the development of transcriptome-trait matching that associates a trait of interest (e.g., GI-tract survival) with transcripts levels that enables the identification of genetic robustness markers, that can be modulated by pre-adaptation and/or genetic engineering to enhance robustness. Furthermore, specific additives to the in situ delivery matrix may enhance the relative tolerance of specific bacterial strains to detrimental conditions they may encounter in different regions of the GI-tract. Moreover, a methodology that allows the molecular quantification of single strains in a mixed bacterial population using engineered sequence-tags or naturally occurring discriminatory intergenic alleles in combination with next-generation sequencing offers another powerful tool for robustness evaluation. Finally, the stress responses of probiotic cultures in relation to improval of their GI persistence and some future directions for development and GI-tract research in the light of probiotic performance are discussed.

14. Biology of Reactive Oxygen Species, Oxidative Stress, and Antioxidants in Lactic Acid Bacteria

Marta C.T. Leite, Bryan Troxell, Jose M. Bruno-Bárcena and Hosni M. Hassan

Lactic acid bacteria (LAB) are important in food fermentations and in human health. Due to their physiological and ecological heterogeneity, they encounter a variety of stressors including acid, osmolality, heat, bile-salt, and oxygen. LAB are exposed to oxidative stress caused by the partially reduced reactive oxygen species (ROS) generated from endogenous sources as well as from the environment. Findings over the past fifty years have demonstrated that this group of organisms comprise a heterogeneous mixture of different genera, where some members of the group have the capacity to synthesis antioxidant enzymes like Mn-containing superoxide dismutase (MnSOD), non-heme catalases (i.e., Mn-containing catalase: MnKat), and heme catalases (when provided with exogenous source of heme). Furthermore, some members of the group can accumulate large intracellular concentrations of manganese to use in the detoxification of ROS. In this chapter, we discuss the natural defenses against ROS in LAB as well as the technological practices used in the food and nutraceutical industries to protect LAB from oxidative stress and loss of viability during processing and storage.

15. Functional Aspects of the Endogenous Microbiota that Benefit the Host

Koen Venema

Over the past 2 or 3 decades we have learned a great deal about our gut microbiota. It is well-established that the microbiota plays a role in just about any disease and disorder that human mankind suffers from. Primarily this is due to the interaction of the microbiota with the host at various levels: i) modulation of the host immune system, which has effects far beyond the local effects in the gut and may reach up to the brain, and ii) production of healthy or toxic microbial metabolites that also may have systemic effects, either directly or after co-metabolism by the host. The composition, and hence the activity of the microbiota, is determined by food and medication. Certain food-components, such as prebiotics, fibers or polyphenols, may lead to production of health-promoting metabolites, while e.g., excess protein may lead to the production or what are generally considered toxic metabolites. Antibiotics and other drugs may influence the (composition and) activity of the microbiota in such as way that the activity has deleterious effects on the host. This review discusses some of the functional aspects of the gut microbiota thought to be important for health of the host. This chapter will review recent insight in the functional role of the microbiota in health and disease.

16. Studying the Microbiota and Microbial Ecology of the Gastrointestinal Tract in the Omics Era: Tools for Stools

Kieran M. Tuohy, Francesca Fava and Nicola Segata

The human gut microbiota is now recognised as an important contributor to host health and disease, with diet:microbe interactions playing critical roles in immune function, energy balance and even brain development and cognitive function. Importantly, these advances in the fields of physiology and nutrition have come at a time when methodologies for studying microbial communities are providing a comprehensive tool-kit of unparalleled resolution and breadth of coverage, allowing for the first time efficacious measurement of important ecological parameters within the gut microbiome. Over the past thirty years a diverse tool kit has been developed, including molecular methods both for targeted microbial quantitation and semi-quantitative but high resolution/broad spectrum methods capable of identifying theoretically all microorganisms within an ecosystem. These methods too allow us to measure both the metabolic potential and metabolic kinetic of the gut microbiota allowing researchers to shed new light on what was until very recently the black hole of microbiota ecological function within the gut. This chapter describes a collection of molecular genetic and metabolomic approaches used to study the human gut microbiota.

17. Metagenomics of the Gut Microbiota as a Tool for Discovery of New Probiotics and Prebiotics

Hyun Ju You, Jiyeon Si and GwangPyo Ko

The human gut is comprised of diverse microbiota, which put substantial impact on various human diseases. The gut microbiota is linked to the maintaining gastrointestinal homeostasis and the association between metabolic and inflammatory diseases such as obesity, type 2 diabetes, low-grade chronic inflammation, and inflammatory bowel disease. Consequentially, the growing interest in gut microbiota has resulted in the development of functional foods such as probiotics and prebiotics, which have been reduce the risk of disease and improve host health. Recent advances in nucleotide sequencing technology widen the profile of the previously unknown microbial communities. International collaborative projects such as the MetaHIT initiative and the Human Microbiome Project (HMP) revealed the diversity of the gut microbiota and their metabolic functions and interactions in the host using this new technique. Current advancement of these tools eases analysis of the massive datasets, yet challenges remain for a complete construction of the microbiome. Here we discuss the development of metagenomics along with the challenges and future perspectives for metagenomic studies to find new probiotics and prebiotics.

18. Emerging Applications of Established Prebiotics: Promises Galore

Seema Patel

Prebiotics are non-digestible food ingredients that invigorate and boost proliferation of health-promoting bacteria in the gastro-intestinal tract, while inhibiting enteric pathogens. The term prebiotics so far encompasses fermentable carbohydrates and oligosaccharides. Prebiotics were catapulted to prominence after their stimulatory role towards bifidobacteria was recognized. They are currently being implicated as sweetener, fat replacer, starter culture formulation, for bacteriocin induction as well as for gut health maintenance, laxative and colitis prevention. However, their functionality has now ramified to multiple significant domains. The unconventional applications have been met with moderate to excellent success viz. cancer inhibition, immune-augmentation, anti-allergic, diabetes control, cholesterol reduction, cardiovascular risk mitigation, obesity management, sepsis prevention, neural protection, vaginal health restoration, bone density increment, guard for kidney ailments, addressing dermatolgical issues, as well as feed additive and antibiotic substitute in aquaculture and veterinary care. The versatile usage of prebiotics has motivated intense research in this field. The exploration of new biological roles for established prebiotics, generation of new compounds from unconventional sources (even extending beyond carbohydrates) and up-grading of existing technology have been identified as promising. This chapter presents in a nutshell, the known prebiotics and their conventional as well as evolving implications for enrichment of food, drugs, and cosmetics and use in the veterinary sector.

19. Prebiotics: Technological Aspects and Human Health

Vanessa Rios de Souza, Camila Carvalho Menezes, Luciana Rodrigues Cunha, Patricia Aparecida Pimenta Pereira and Uelinton Manoel Pinto

Prebiotics are known as selectively fermented ingredients that allow modifications in the composition and/or activity of the gastrointestinal microbiota conferring benefits to the host wellbeing. They are commonly described as short-chain carbohydrates containing between two and sixty monosaccharides, which are not digested by human or animal enzymes making them selectively fermented by specific beneficial colon bacteria. Besides promoting the intestinal microbiota, they also prevent the incidence of gastrointestinal infections, modulate the immune system, increase the bioavailability of minerals, regulate metabolic disorders related to obesity and diabetes and decrease the risk of cancer. In addition to the functional characteristics, the use of prebiotics by the food industry has been prompted by their favorable technological aspects. In this chapter we present the main functional and technological aspects of inulin, fructo-oligosaccharides (FOS), lactulose, galactoligosaccharides (GOS), resistant starch (RS), soybean oligosaccharides (SOS), xylooligosaccharides (XOS) and isomaltooligosaccharides (IMO).

20. New and Tailored Prebiotics: Established Applications

Shanthi G. Parkar, Paul A. Blatchford, Caroline C. Kim, Douglas I. Rosendale and Juliet Ansell

‘Prebiotics' have been recognised for nearly 20 years, and have recently been defined as selectively fermented ingredients that that modulate the gut microbial composition and/or activity to deliver benefits to human health, through a range of host and microbial derived mediators. Here, we discuss the emerging range of biomolecules with potential prebiotic properties beyond the well-characterised galacto- and fructo-oligosaccharides. These include carbohydrate-based foods that provide accessible glycoside substrates to the gut microbiome, polyphenols and glucosinolates, which comprise both fermentable sugar moieties and/or alternative phytochemical-based substrates. We examined the microbial and molecular responses to potential prebiotics that validate their benefits to host health in terms of the ability of the prebiotics to alter the gut microbiome and the molecular responses that mediate the link between prebiotics and established host benefits including improved gastrointestinal function.

21. Immunomodulating Effects of Prebiotics and Fibres

Hanne Frøkiær, Stine Broeng Metzdorff and Koen Venema

The beneficial effects of fibres have long been attributed to their bulking effect, reducing the transit time of chyme through the gastrointestinal (GI) tract, thereby e.g. reducing the contact of potential toxic compounds with the gastrointestinal epithelium and preventing constipation. Lately however, it has been recognized that fibres may have prebiotics effects by modulating the activity of the gut microbiota, and even direct effects on the immune system. This chapter highlights the effects of fibres on the immune system. Mostly direct interactions with the host are discussed, although effects of microbial fermentation products (the so-called short-chain fatty acids [SCFA]) on the immune system is also briefly mentioned.

22. Prebiotics Beyond Fibers

Delphine M. Saulnier and Michael Blaut

The research on the potential prebiotic properties of polyphenols, human milk oligosaccharides (HMOs), polypeptides and polyols - bioactive compounds not being strictly defined as fibers - has increased at a rapid pace. A selective stimulation of members of the microbiota traditionally associated with health benefits, such as bifidobacteria and lactobacilli, and an inhibition of potentially pathogenic species, has been demonstrated in vitro for most of these compounds. Evidence for health benefits associated with microbiota changes have started to emerge for polyphenols and HMOs in animal studies. An improvement of biomarkers for type-2 diabetes accompanied by an increase in bifidobacteria and lactobacilli occurred in a limited number of healthy subjects in response to the intake of polyphenols. Well-designed double-blind placebo controlled nutritional intervention studies should be conducted to confirm or refute a causal link between changes in microbiota composition and an improvement of type-2 diabetes or obesity. Here we present and discuss our perception of the future trends that we foresee in this field, and provide some recommendations for future research.

23. Synbiotics: More Than Just the Sum of Pro- and Prebiotics?

Koen Venema

This is a comprehensive but critical overview of the studies performed with synbiotics (products containing both probiotics and prebiotics) up to date. Most of the studies reviewed did not have the desired controls, i.e. arms with only the probiotic or only the prebiotic. This makes it impossible to judge whether the synbiotic (that is the combination of both probiotics and prebiotics) was required for the observed effect, or whether one of the components alone would have done the trick as well. Studies in adults, children and elderly, with and without disorders or diseases are highlighted. Only human trials are discussed, although a few in vitro studies and studies in experimental animals are reviewed to highlight potential mechanisms of action.

24. Pro- and Prebiotics: The Role of Gut Microbiota in Obesity

Marc R. Bomhof and Raylene A. Reimer

Obesity is a multifactorial disease that is widespread and continuing to increase in prevalence worldwide. The composition of the gut microbiota is altered in obesity and is associated with impaired gut barrier, enhanced proinflammatory response and metabolic disturbances. Manipulation of the gut microbiota as a therapeutic intervention in obesity and other chronic diseases is of major interest. Diet plays a major role in shaping the composition of the gut microbiota and prebiotics and probiotics have received much attention in this regard. This chapter examines the evidence for the effect of prebiotics and probiotics on obesity with special attention given to body weight and adiposity, appetite regulation, inflammation and gut barrier integrity and glucose and lipid metabolism.

25. The Role of the Gut Microbiota in Brain Function

Julia König, John-Peter Ganda Mall, Ignacio Rangel, Hanna Edebol and Robert-Jan Brummer

The intestinal microbiota forms a complex ecosystem that has an important impact on our health, and an increasing number of disorders are associated with disturbances in this ecosystem. There is growing evidence that even brain function can be affected by an aberrant gut microbiota and that the bidirectional signalling along the microbe-gut-brain axis plays a significant role in the well-being of the gut as well as the brain. In this chapter, mechanistic pathways explaining how the gut microbiota can affect brain function are described. In addition, its role is elucidated in relation to disorders such as anxiety, depression, autism spectrum disorder, Parkinson's disease and Alzheimer's disease, and possible beneficial action of prebiotics and probiotics is discussed.

26. Infant Development, Currently the Main Applications of Probiotics And Prebiotics?

Giuseppe Mazzola, Irene Aloisio and Diana Di Gioia

Research on probiotics and prebiotics for use in infants is very active and results on their efficacy to prevent and combat several diseases are at present available. Bifidobacteria and lactobacilli are considered beneficial bacteria for the gut, the former being the predominant group of healthy breast-fed newborns. One of the major area of probiotic research in children has been the treatment and prevention of diarrhea. Moreover, a large number of infant pathologies, both enteric (infantile colics, necrotizing enterocolitis, celiac disease) and not strictly enteric (allergies, obesity, neurologic disease) have revealed promising preventive and therapeutic effects of probiotics, although these applications need additional experimental evidences. Recent studies have shown that probiotic strain characteristics are crucial to reach a targeted therapeutic effect. One of the major aspect affecting the gut microbial composition of breast-fed neonates is the presence of oligosaccharides in breast milk. These molecules exert a prebiotic effect which is crucial for the development of a healthy gut microbiota. Research studies have been focused on the selection of fibers possessing a prebiotic role similar to human milk oligosaccharides. Galactooligosaccharides and fructoligosaccharides are abundantly used in infant formula, frequently as mixtures of the two molecules. Several studies have shown that the capability of stimulating beneficial bacteria and of shaping the gut microbiota is similar to that of breast milk. On the contrary, studies regarding the use of prebiotics in infants for the prevention of allergies showed contradictory results. Therefore, it is possible to conclude that children are a very important target, if not the main one, for probiotic and prebiotic administration and the European industry is aware of that.

27. Pro- and Prebiotics in Management of Patients with Irritable Bowel Syndrome

Ratnakar Shukla, Ujjala Ghoshal and Uday C. Ghoshal

Recently, several studies suggested that altered quantity and quality in gut microbiota, called dysbiosis, are important in the pathogenesis of irritable bowel syndrome (IBS). It is therefore worthwhile to evaluate whether therapeutic manipulation of the gut microbiota using probiotics would be effective and safe in management of these patients. Several studies showed that probiotics are effective in manipulation of altered gut microbiota and in improving the global IBS symptoms. Probiotics reduce visceral hypersensitivity, improve colonic transit time, enhance the intestinal epithelial barrier, modulate immune response via production anti-inflammatory and regulatory cytokines, and thus, inhibit the inflammation. Prebiotics, which are sometimes added to probiotics (symbiotics) improve the fermentation pattern, stool consistency, abdominal pain and bloating and flatulence in patients with IBS. Several meta-analyses have confirmed the efficacy of probiotics in management of IBS. Hence, it can be concluded that probiotics are useful in treatment of IBS, particularly diarrhea predominant subtypes, and most studies showed that abdominal pain, bloating and flatulence are the symptoms, which were relieved most.

28. Pro- and Prebiotics for Oral Health

Svante Twetman, Mette Rose Jørgensen and Mette Kirstine Keller

Recent insights in the importance of a natural microbial balance in the oral biofilm for maintaining health have brought a new concept to dentistry; to prevent ecologically disruptions rather than merely treating its consequences by restoring cavities. Consequently, an emerging interest in the use of probiotic bacteria for oral health is evident, albeit the local and systemic mechanisms of actions are still largely unknown. This chapter provides a brief background on the role of the oral biofilm in health and disease and examines the evidence for probiotic therapy within dentistry, based on clinical trials. Several studies have displayed an antagonistic role of probiotic lactobacilli and bifidobacteria against salivary Streptococcus mutans and four studies have shown reduced caries incidence and root caries arrest. Other trials have reported beneficial effects on endpoints related to gingivitis and periodontitis such as plaque index, gingival index, probing depth, subgingival microbiota and pro-inflammatory cytokine levels in gingival crevicular fluid. No adverse effects have been reported but further research is needed to confirm findings and strengthen the evidence before clinical recommendations can be advocated.

29. Cholesterol-lowering Effects of Probiotics and Prebiotics

Min-Tze Liong, Byong-H. Lee, Sy-Bing Choi, Lee-Ching Lew, Amy-Sie-Yik Lau and Eric Banan-Mwine Daliri

Recently, the use of probiotics and prebiotics as a cholesterol lowering agent has become increasingly popular. This chapter will highlight some of the in vitro and in vivo evidence showing the potential of probiotics and prebiotics in improving serum lipid profile. Data revealing details at molecular levels has also been included in this chapter. The proposed mechanisms for cholesterol removal by probiotics include assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface and incorporation into the cellular membrane, deconjugation of bile via bile salt hydrolase, coprecipitation of cholesterol with deconjugated bile and production of short-chain fatty acids from oligosaccharides. In this chapter, we have highlighted on a few more selected cholesterol lowering mechanisms that are feasible and supported by in-depth evidence. Although cholesterol lowering abilities of probiotics has been extensively reported; recently, controversies have risen attributed to the activities of deconjugated bile acids that repress the synthesis of bile acids from cholesterol. Using a molecular docking approach, we have demonstrated that deconjugated bile acids have higher binding affinity towards some orphan nuclear receptors namely the farsenoid X receptor (FXR), leading to a suppressed transcription of the enzyme cholesterol 7-alpha hydroxylase (7AH), which is responsible for bile acid synthesis from cholesterol. Possible detrimental effects due to increased deconjugation of bile salts such as malabsorption of lipids, colon carcinogenesis, gallstones formation and altered gut microbial populations, which contribute to other varying gut diseases, are also included in this chapter. The effects of probiotics and prebiotics on other cholesterol-related disorders such as formation of abnormal erythrocytes are also discussed in this chapter. As described in the past studies, hypercholesterolemia could induce alterations in the human erythrocyte plasma membrane. Administration of probiotics and prebiotics has improved erythrocyte membrane fluidity, decreased membrane rigidity and altered membrane lipid profiles. Probiotics and prebiotics is a new feasible approach to use natural interventions for cholesterol management.

30. Perspectives on Differences Between Human and Livestock Animal Research in Probiotics and Prebiotics

Tyler E. Askelson and Tri Duong

Probiotics and prebiotics are used widely because of their reported benefits to digestive and immune health. While there is significant evidence to support their effectiveness in humans and livestock animals, interpretation of the results of this research is complicated by the wide differences in research performed in humans as compared to livestock animals. This chapter will explore host-specific digestive physiology, experimental constraints, and probiotic and prebiotic functionality. The insight provided by an understanding of these critically important differences will provide a context in which results of host-specific studies and their broader implications to the science can be evaluated.

31. The Use of Probiotics to Enhance Animal Performance

Juliana Teixeira de Magalhães, Luciene Lignani Bitencourt, Marta Cristina Teixeira Leite, Ana Paula do Carmo and Célia Alencar de Moraes

Enteric infections by pathogenic bacteria and clinical expression of disease occur frequently in young animals. Multiple environmental changes usually lead to stressful conditions and trigger transitory inflammatory responses in the gut that can contribute to anatomical and functional intestinal disorders (Berge and Wierup, 2011; Heo et al., 2013; Suda et al., 2014). These diseases have often brought about significant economic losses in animal production. In order to solve this problem, antibiotics have been included in animal feeds either at sub-therapeutic levels (acting as growth promoters-AGPs), or at therapeutic levels, to treat diseases. As growth promoters, they reduce competition for nutrients between the gastrointestinal (GI) microbiota and the host. The effects of such competition have often been at the cost of animal performance. Unfortunately, there has been considerable concern over the use of AGP's, because their long term and extensive use in animal production has resulted in selection for survival of resistant bacterial species or strains (Van der Fels-Klerx et al., 2011; Thaker, 2013). Moreover, consumer demand for organic and natural food continues to increase in the world because of an ongoing perception that organic or natural products are better than their conventional counterparts in terms of safety, taste, and increased health benefits. The general term organic foods is used to define foods that are produced without using chemical fertilizers, additives, and synthetic pesticides as well as not being processed with irradiation. Among organic foods, the overall organic meat market size is small compared with the conventional meat industries. However, according to the Organic Trade Association, the organic meat industry has grown $ 3.8 billion in 2014 (OTA, 2014). In general, with increases in organic meat products, new management approaches are needed to compensate for potential food safety concerns and animal health. Thus, the use of probiotics have been suggested as the most desirable alternative for livestock due to their beneficial effects. Probiotic bacterial species are included in the diet to promote health, protecting the intestine against pathogenic microorganisms and reducing inflammation (Ross et al., 2010; Meng et al., 2014, Cho et al., 2011; Thacker, 2013). This chapter will focus the use of probiotics as a feed additive discussing their beneficial effects in swine, poultry, aquaculture and ruminants.

32. Pharmaceutical Aspects of Probiotics and Prebiotics

Indu Pal Kaur, Parneet Kaur Deol, Simarjot Kaur Sandhu and Parveen Rishi

In recent times, increasing evidence of benefits of probiotics, for health restoration coupled with consumer's inclination towards safe, natural, and cost effective substitutes for drugs, has generated immense interest in exploring their therapeutic potential. Administering probiotics as such not only compromises their viability but also fails to guarantee their successful establishment in gut. In recent times emphasis has been made to take a pharmaceutical approach to probiotics which will not only maintain their viability during storage but will also assist in their successful delivery to and establishment at the site of action in a viable form. Further to above, supplementation of probiotics with prebiotics is also gaining predominance in the recent past. Numerous reports indicate that co-encapsulating prebiotics with probiotics, improves viability of the latter, apart from the independent growth promoting effect of the former on the inherent healthy gut microbiota of the host. The current chapter aims to analyze probiotics as pharmaceuticals, their encapsulation techniques, existing pharmaceutical preparations, their regulatory status in some countries, and future research needs. The current status of prebiotics in health care is also highlighted.

33. Is The Sky The Limit?

Koen Venema and Ana Paula do Carmo

Over the past two decades significant progress has been made in both the probiotics and the prebiotics area. Whereas earlier the primary diseases for probiotics were inflammatory bowel disease and allergy, this has now expanded to multiple other diseases and disorders too. And whereas earlier a prebiotic effect was considered to be synonymous with an increase in bifidobacteria, the research field now encompasses much more, and for instance looks at butyrate production, or levels of Faecalibacterium prausnitizii or Akkermansia muciniphila. One can therefore wonder: Are pro- and prebiotics effective for everything? This chapter hypothesizes on aspects that are beginning to be addressed, or have not even been considered yet, but might become relevant in the future as well.

34. Appendix: Web Resources