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Journal ArticleDOI

Health benefits and health claims of probiotics: bridging science and marketing

TL;DR: An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.
Abstract: Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.

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Dissertation
01 Nov 2017
TL;DR: The gut microbiota as a therapeutic approach for gastrointestinal disorders and experimental evidence for the role of the gut microbiota in celiac disease pathogenesis are studied.
Abstract: ...................................................................................................................... iii ACKNOWLEDGMENTS ................................................................................................ vi TABLE OF CONTENTS ................................................................................................ vii LIST OF FIGURES ........................................................................................................ xii LIST OF TABLES .......................................................................................................... xvi LIST OF ABBREVIATIONS ....................................................................................... xvii CHAPTER 1: INTRODUCTON ...................................................................................... 1 1.1 The gastrointestinal immune system ......................................................................... 2 1.1.1 Innate mucosal immunity .................................................................................... 2 1.1.2 Adaptive mucosal immunity ................................................................................ 8 1.1.3 Tolerance to luminal antigens............................................................................ 11 1.2 The intestinal microbiota .......................................................................................... 15 1.2.1 The landscape of the intestinal microbiota ........................................................ 15 1.2.2 Dysbiosis and gastrointestinal disorders ........................................................... 17 1.2.3 Interactions between the mucosal immune system and intestinal microbiota .. 21 Justin L. McCarville – Ph.D. Thesis McMaster University – Medical Science viii 1.2.4 Targeting the intestinal microbiota as a therapeutic approach for gastrointestinal disorders ............................................................................................ 23 1.3 Celiac disease ............................................................................................................. 24 1.3.1 The adaptive immune response in celiac disease .......................................... 25 1.3.2 The innate immune response in celiac disease.............................................. 29 1.3.3 Modulation of celiac disease development and severity ............................... 33 1.4 Treatment of celiac disease........................................................................................ 33 1.5 The gut microbiota in celiac disease ......................................................................... 34 1.5.1 Clinical associations of the gut microbiota and celiac disease .................... 34 1.5.2 Experimental evidence for the role of the gut microbiota in celiac disease pathogenesis. .......................................................................................................... 37 1.5.3 Digestion of gluten by gastrointestinal bacteria ........................................... 40 1.6 Proteases and protease inhibitors in the gastrointestinal tract ............................ 41 1.6.1 Proteolytic balance in the gastrointestinal tract ........................................... 41 1.6.2 Recognition of proteases by protease activated receptors (PARs) ............... 43 1.6.3 Proteolytic imbalances in IBD and functional bowel disorders ................... 45 1.6.4 Proteolytic imbalance in celiac disease ........................................................ 48 1.6.5 Bacteria as a source of proteases and protease inhibitors ............................ 49 1.6.6 Bacteria as contributors of proteolytic imbalances in gastrointestinal disorders ................................................................................................................ 51 Justin L. McCarville – Ph.D. Thesis McMaster University – Medical Science ix CHAPTER 2: THESIS OBJECTIVES .......................................................................... 54 THESIS SCOPE ..................................................................................................... 55 THESIS AIMS ...................................................................................................... 56 CHAPTER 3: DUODENAL BACTERIAL FROM PATIENTS WITH CELIAC DISEASE AND HEALTHY SUBJECTS DISTINCTLY AFFECT GLUTEN BREAKDOWN AND IMMUNOGENICITY ................................................................ 59 SUMMARY .......................................................................................................... 60 ABSTRACT .......................................................................................................... 64......................................................................................................... 64 INTRODUCTION ................................................................................................ 66 METHODS ........................................................................................................... 67 RESULTS ............................................................................................................. 74 DISCUSSION ........................................................................................................ 92 ACKNOWLEDGMENTS .................................................................................... 97 REFERENCES ..................................................................................................... 98 SUPPLEMENTARY MATERIALS .................................................................. 105 CHAPTER 4: MICROBIAL PROTEASES MODULATE INNATE IMMUNITY AND INCREASE SENSITIVITY TO DIETARY ANITGEN THROUGH PAR-2 119 SUMMARY ........................................................................................................ 120 ABSTRACT ........................................................................................................ 124....................................................................................................... 124 Justin L. McCarville – Ph.D. Thesis McMaster University – Medical Science x INTRODUCTION .............................................................................................. 125 METHODS ......................................................................................................... 127 RESULTS ........................................................................................................... 133 DISCUSSION ...................................................................................................... 133 ACKNOWLEDGMENTS .................................................................................. 146 SUPPLEMENTARY FIGURES ......................................................................... 150 REFERENCES ................................................................................................... 156 CHAPTER 5: A COMMENSAL BIFIDOBACTERIUM LONGUM STRAIN IMPROVES GLUTEN-RELATED IMMUNOPATHOLOGY IN MICE THROUGH EXPRESSION OF A SERINE PROTEASE INHIBITOR ....................................... 161 SUMMARY ........................................................................................................ 162 ABSTRACT ........................................................................................................ 166....................................................................................................... 166 INTRODUCTION .............................................................................................. 167 METHODS ......................................................................................................... 169 RESULTS ........................................................................................................... 178 DISCUSSION ...................................................................................................... 190 ACKNOWLEDGMENTS .................................................................................. 195 REFERENCES ................................................................................................... 196 SUPPLEMENTARY FIGURES ......................................................................... 199 Justin L. McCarville – Ph.D. Thesis McMaster University – Medical Science xi DISCUSSION ................................................................................................................ 208 6.1 Summary ................................................................................................................... 209 6.2 Commensal-derived proteases metabolize gluten producing peptides with different immunogenicity .............................................................................................. 211 6.3 Commensal-derived proteases trigger intestinal inflammation and exacerbate pathology ......................................................................................................................... 214 6.4 Delivery of a protease inhibitor by a commensal bacterium prevents gluteninduced pathology ......................................................................................................... 218 6.5 Future Directions .................................................................................................... 220 6.6 Conclusions ............................................................................................................... 221 REFERENCES ............................................................................................................... 225 APPENDIX I: NOVEL PERSPECTIVES ON THE HERAPEAUTIC MODULATION OF THE GUT MICROBIOTA ...................................................... 240 APPENDIX II: PHARMACOLOGICAL APPRAOCHES IN CELIAC DISEASE .......................................................................................................................................... 255 APPENDIX III: INTESTINAL MICROBIOTA MODULATES GLUTENINDUCE

5 citations

Journal ArticleDOI
TL;DR: The most common techniques used for microencapsulation of probiotics will be presented, as well as the most usual microcapsule shell materials.
Abstract: Probiotics are viable microorganisms widely used for their claimed beneficial effects on the host health. A wide number of researchers proved that the intake of probiotic bacteria has numerous health benefits which created a big market of probiotic foods worldwide. The biggest challenge in the development of these products is to maintain the viability of bacterial cells during the storage of the product as well as throughout the gastrointestinal tract transit after consumption, so that the claimed health benefits can be delivered to the consumer. Different approaches have been proposed for increasing the resistance of these sensitive microorganisms, including the selection of resistant strains, incorporation of micronutrients, and most recently the use of microencapsulation techniques. Microencapsulation has resulted in enhancing the viability of these microorganisms which allows its wide use in the food industry. In this review, the most common techniques used for microencapsulation of probiotics will be presented, as well as the most usual microcapsule shell materials.

4 citations

Book ChapterDOI
01 Jan 2018
TL;DR: This chapter discusses therapeutic strategies that utilize pro- and prebiotic treatments, as means to promote normal microbiota balance and maintain normal local GI functions, while potentially intervening in inflammation-based conditions.
Abstract: Dysbiosis of the intestinal microbiota making up the human microbiome can have a profound influence on energy and immune homeostasis, which result in significant metabolic and immunologic effects on the host, ultimately leading to many local and systemic diseases. Diet, as it contains components that provide energy to the host microbiota, plays a significant role in the maintenance of the complex microbiome. High-fat and high sugar diets, and diets that are low in fermentable fiber lead to dysbiosis, while diets low in fat and sugar, and high in fermentable fiber, particularly prebiotic fiber, can significantly promote proper energy homeostasis and immune response to reduce disease risk and promote overall health. In healthy condition, dietary modification, as well as treatment with pro- and prebiotic use, can help maintain proper microbiota balance and promote proper energy and immune homeostasis. In a dysbiotic condition, dietary modification, as well as treatment with pro- and prebiotics, and, in more severe cases, complete restoration of fecal microbiota through stool transplantation, may help intervene in a disease state. This chapter discusses therapeutic strategies that utilize pro- and prebiotic treatments, as means to promote normal microbiota balance and maintain normal local GI functions, while potentially intervening in inflammation-based conditions. In addition, fecal microbiota transplantation is discussed as therapy to intervene in more severe infections or inflammatory conditions.

4 citations

Journal ArticleDOI
Cecilia Leal1
TL;DR: In this article , basic knowledge with regard to the gut-liver axis, available probiotics remedies and mechanistic insights of S. boulardii as probiotic will be elucidated.
Abstract: Saccharomyces boulardii (S. boulardii) is a probiotic yeast that has been elucidated to be efficacious in fighting various gastrointestinal diseases in preclinical as well as clinical studies. Its general mechanisms of probiotic action in the treatment of gastrointestinal conditions cover multifaceted aspects, including immune regulation, production of antimicrobial substances, pathogen competitive elimination, gut barrier integrity maintenance, intestinal trophic effect and antioxidant potency. In this review, basic knowledge with regard to the gut-liver axis, available probiotics remedies and mechanistic insights of S. boulardii as probiotics will be elucidated. In addition, we summarize the therapeutic potential of S. boulardii in several liver diseases evident from both bench and bedside information, such as acute liver injury/failure, fibrosis, hepatic damages due to metabolic disturbance or infection and obstructive jaundice. Future prospects in relation to medicinal effects of S. boulardii are also exploited and discussed on the basis of novel and attractive therapeutic concept in the latest scientific literature.

4 citations

References
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Journal ArticleDOI
04 Mar 2010-Nature
TL;DR: The Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals are described, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species.
Abstract: To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively

9,268 citations


"Health benefits and health claims o..." refers background in this paper

  • ...For the fifty-seven most common bacterial species identified by metagenome sequence analysis in the human gut, the inter-individual variability of abundance is between 12- and 2187-fold((16))....

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  • ...However, a clearly distinct composition of gut microbiota, both compared with healthy individuals and between the two diseases, is found in inflammatory bowel disease (ulcerative colitis and Crohn’s disease)((16))....

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Journal ArticleDOI
29 May 2008-Nature
TL;DR: It is reported here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus and that molecules of the bacterial microbiota can mediate the critical balance between health and disease.
Abstract: Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

2,097 citations


"Health benefits and health claims o..." refers background in this paper

  • ...In a series of landmark publications((7,19,20)), Dennis Kasper’s group has demonstrated that the capsular polysaccharide polysaccharide A of Bacteroides fragilis is indispensable for normal development of mucosal T lymphocytes and control of exper-...

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  • ...Unfortunately, with a few exceptions((7,8)), the genes that determine or underlie the health benefit delivered by specific probiotic strains have not been identified to date....

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Journal ArticleDOI
17 May 2010-PLOS ONE
TL;DR: Evidence is provided for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system, because of its crucial role in the host physiology and health status.
Abstract: Background: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians’ microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host’s immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

1,180 citations


"Health benefits and health claims o..." refers background in this paper

  • ...Moreover, the intestinal microbiota also changes in time as was illustrated recently in a study, in which age groups up to 100 years were compared((17))....

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Journal ArticleDOI
TL;DR: The nonclassic actions of vitamin D are cell specific and provide a number of potential new clinical applications for 1,25(OH)(2)D(3) and its analogs, however, the use ofitamin D metabolites and analogs for these applications remains limited by the classic actions of Vitamin D leading to hypercalcemia and hypercalcuria.
Abstract: Context: Vitamin D receptors are found in most tissues, not just those participating in the classic actions of vitamin D such as bone, gut, and kidney. These nonclassic tissues are therefore potential targets for the active metabolite of vitamin D, 1,25(OH)2D. Furthermore, many of these tissues also contain the enzyme CYP27B1 capable of producing 1,25(OH)2D from the circulating form of vitamin D. This review was intended to highlight the actions of 1,25(OH)2D in several of these tissues but starts with a review of vitamin D production, metabolism, and molecular mechanism. Evidence Acquisition: Medline was searched for articles describing actions of 1,25(OH)2D on parathyroid hormone and insulin secretion, immune responses, keratinocytes, and cancer. Evidence Synthesis: Vitamin D production in the skin provides an efficient source of vitamin D. Subsequent metabolism to 1,25(OH)2D within nonrenal tissues differs from that in the kidney. Although vitamin D receptor mediates the actions of 1,25(OH)2D, regulati...

882 citations

Journal ArticleDOI
TL;DR: This Review highlights the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs with respect to host pattern recognition receptors of the gastrointestinal mucosa.
Abstract: Interactions between host cell receptors and the surface molecules of bacteria are important determinants of the nature of the relationship between the two organisms. In this Review, Lebeer, Vanderleyden and De Keersmaecker examine the signalling interactions of probiotic bacterial cell surface molecules. How can probiotic bacteria transduce their health benefits to the host? Bacterial cell surface macromolecules are key factors in this beneficial microorganism–host crosstalk, as they can interact with host pattern recognition receptors (PRRs) of the gastrointestinal mucosa. In this Review, we highlight the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs. Research on host–probiotic interactions can benefit from well-documented host–microorganism studies that span the spectrum from pathogenicity to mutualism. Distinctions and parallels are therefore drawn with the interactions of similar molecules that are presented by gastrointestinal commensals and pathogens.

852 citations


"Health benefits and health claims o..." refers background in this paper

  • ...For a number of strains, it has been demonstrated now that the probiotic bacteria can bind to receptors on cells of the immune system including dendritic cells((27))....

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