Diet-Microbe Interactions in the Gut

Effects on Human Health and Disease

Kieran Tuohy, Daniele Del Rio

• Publisher: Academic Press
• Year: 2014
• Print ISBN: 9780124078253
• eBook ISBN: 9780124079410
• Topic: Medicine
• Subtopic: Pharmacology

Drawing on expert opinions from the fields of nutrition, gut microbiology, mammalian physiology, and immunology, Diet-Microbe Interactions for Human Health investigates the evidence for a unified disease mechanism working through the gut and its resident microbiota, and linking many inflammation-related chronic diet associated diseases.State of the art post-genomic studies can highlight the important role played by our resident intestinal microbiota in determining human health and disease. Many chronic human diseases associated with modern lifestyles and diets — including those localized to the intestinal tract like inflammatory bowel disease and celiac disease, and more pervasive systemic conditions such as obesity, diabetes and cardiovascular disease — are characterized by aberrant profiles of gut bacteria or their metabolites. Many of these diseases have an inflammatory basis, often presenting with a chronic low-grade systemic inflammation, hinting at persistent and inappropriate activation of inflammatory pathways.Through the presentation and analysis of recent nutrition studies, this book discusses the possible mechanisms underpinning the disease processes associated with these pathologies, with high fat diets appearing to predispose to disease, and biologically active plant components, mainly fiber and polyphenols, appearing to reduce the risk of chronic disease development. - One comprehensive, translational source for all aspects of nutrition and diet's effect on gastrointestinal health and disease - Experts in nutrition, diet, microbiology and immunology take readers from the bench research (cellular and biochemical mechanisms of vitamins and nutrients) to new preventive and therapeutic approaches - Clear presentations by leading researchers of the cellular mechanisms underlying diet, immune response, and gastrointestinal disease help practicing nutritionists and clinicians (gastroenterologists, endocrinologists) map out new areas for clinical research and structuring clinical recommendations

Chapter 1

The Microbiota of the Human Gastrointestinal Tract

A Molecular View

Kieran M. Tuohy* and Karen P. Scott^†, *Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all’Adige, Trento, Italy, ^†The Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB. United Kingdom

The human gut microbiota represents a complex collection of microorganisms, which contribute considerably to host health. They occupy different ecological niches and habitats within the gastrointestinal tract and vary both in compositional make up and metabolic output at different sites along the gut. In this chapter, we describe the microbial “geography” within the human gastrointestinal tract and discuss available methods for studying the gut microbiota at both taxonomic and metabolic levels. Tremendous advances have been made in culture independent molecular microbiology over the past 20 years giving previously undreamt of insight into the architecture of the gut microbiota. Similarly, advances in “omics” technologies, especially metagenomics and metabolomics, are providing the tools necessary to give, for the first time, a real insight into both the gut microbiota metabolic potential (encoded by the genes of microbiota metagenome) and the metabolic kinetic (comprising the flux of microbially derived metabolites) and how these then interact with host physiology influencing health and disease risk.

Keywords

Gut microbiota; Stomach; Small intestine; Colon; PCR; FISH; Metagenomics; Metabonomics; Metabolomics; Gut models

Introduction

All multicellular organisms with an organized intestine carry an intestinal microbiota. The gut microbiota serves a number of important functions: providing nutrients to the host, aiding in the digestion of complex food components, providing a barrier to invading pathogenic microorganisms, and in higher animals at least, helping to maintain immune homeostasis.^1,2 This closely co-evolved partnership comes at a cost in terms of energy, with carriage of a diverse microbiota of many hundreds of different microbial species and complex populations in the colon reaching 10¹¹ cells/g contents necessitating maintenance of costly host defences. The gut-associated lymphoid tissue (GALT) is the single largest immune organ in the body and is designed to recognize microbial friend from foe and to keep this complex microbial ecosystem in check, it expends considerable energy to safely accommodate the gut microbiota and fight off invading pathogens.² However, in health at least, this cost is greatly offset by microbial biotransformation of complex plant foods into intermediates, especially fermentation end products, which can then be absorbed and metabolized by the host. For example, early estimates put the contribution of microbial fermentation in terms of short-chain fatty acids (SCFA) made available to the host at about 10% daily human energy demand.^3,4 From the microbial point of view of course, this energy balance equation looks quite different, with the host, either directly through secretions of the gastrointestinal tract (sloughed off epithelial cells, digestive enzymes and mucin and other glycoproteins from the mucus layer covering the gut wall) or indirectly through ingested food, providing a continuous supply of energy and nutrients, and also a relatively stable ecological habitat with the potential for potentiation and transfer into new hosts once the current host “passes away.”

Gut Microbiota Metabolism in Health and Disease

Living with a complex gut microbiota means living at the precipice of “war and peace.” As in most conflicts, energy availability and ownership, and miscommunication (e.g., inability of the host’s immune system to respond appropriately to commensal microorganisms) decide the balance of power, leading to health or disease. Indeed, it is becoming clear that the human gut microbiota plays a critical role in human health, with battlegrounds revolving about metabolism and immune function.^5–7 Diet is a major external force, acting on both human disease risk and gut microbiota function.^8,9 The gut microbiota, depending on dietary intake and consequently nutrient availability within the gut, can produce either harmful metabolites linked to human disease or beneficial compounds that protect against host disease. For instance both the conversion of ingested xenobiotic compounds into carcinogens and genotoxins, and the production of trimethylamines have negative effects, while the production of SCFA, vitamins (vitamin K and B vitamins including cobalamin, folate, niacin, thiamine) and conjugated linoleic acids (CLA), have positive health benefits.^5,8–15 In some cases, distinct metabolic pathways have been associated with bacteria we consider beneficial for human health. Some bifidobacteria have been shown to produce folate, and lactobacilli and bifidobacteria species are capable of producing CLA or gamma-aminobutyric acid (GABA) within the gut.^15–18 In many cases we do not know the specific bacterial species involved in metabolite production, and for many metabolites more than one microbial species might be involved.¹⁹ We do know that diet, especially the amount of fermentable fiber and polyphenols reaching the colon, greatly impacts on both the relative abundance of bacteria present and on their metabolic activities.^1,9,20,21 The mammalian gut microbiota is predominantly fermentative, with the fermentation of dietary carbohydrates representing the principle mode of energy conversion within the gut ecosystem, providing energy and carbon sources for fermentative species themselves and supporting a complex food web whereby the end product of one microorganism is the growth substrate for another and of course, the human host.¹² The majority of this dietary carbohydrate is in the form of dietary fiber, a broad term covering many dietary components that escape digestion in the upper gut.²¹ Dietary fiber mainly comprises of resistant starch and other complex polysaccharides of plant origin for which the human genome encodes few hydrolytic enzymes, necessitating extra-genomic aid from our internal microbial symbionts.^22,23 The gut microbiota cleaves complex polysaccharides using an array of glycases, which often work in synergy even when encoded by different microorganisms, releasing smaller oligosaccharides and sugars which are then fermented into SCFA.^4,9,12 The availability of a ready supply of dietary fiber supports a stable microbial consortium mainly involved in saccharolytic fermentation, the end products of which are beneficial to host health.¹ Indeed, this fits neatly with human epidemiological data showing that diets rich in fiber are inversely related to chronic human diseases, especially diseases linked to metabolism and immune function.^24–26 On the contrary, when fermentable carbohydrate is in short supply, the resident microbiota turn to other sources of energy to support growth and changes occur, both in microbial composition and metabolic activity. Fermentation of amino acids is energetically less favorable than carbohydrate fermentation, yet some microorganisms will ferment amino acids derived from endogenous or dietary protein^12,27 releasing end products which are potentially harmful to human health and have been linked to diseases such as cardiovascular disease and colon cancer.^10,28–30 Although most dietary fat will be absorbed in the upper gut, some can reach the colon. Bacteria are poor utilizers of lipids under anaerobic conditions and derive little energy from the conversion of dietary lipids into either beneficial or harmful fatty acids.^15,31,32 However, high-fat diets, both in animal models and in humans, lead to major shifts in the microbial ecology of the gut, to the detriment of beneficial, saccharolytic bacteria.^33–37 Thus although high-fat, low-fiber, diets may provide excess energy to the human host they effectively starve the gut microbiota and contribute to the establishment of aberrant microbiota profiles shown to increase the risk of metabolic and autoimmune disease.³⁸

Dietary modulation of the gut microbiota does not go unnoticed by the guardian of human health, the immune system.^{33,34,38–40} Inflammation, both at the gut wall and systemically, occurs in response to aberrant microbiota within the gut and also with leakage of inflammatory molecules from the gut.^33,34,38 The barrier function of the gut wall appears to be critically determined by the presence of certain key bacterial species and by microbial metabolites like the SCFA butyrate, which serves both as the main energy supply for the intestinal mucosa and as a mediator of gut wall development and differentiation.^41–46 Similarly, microbial metabolites produced by beneficial gut bacteria including acetate, butyrate, propionate, GABA, CLA, all play a role in the optimal functioning of immune cells including first responders like dendritic cells, neutraphiles, macrophages and intestinal epithelial cells. These cells play an important communication role, signaling changes within the gut lumen and directing appropriate responses from immune mediator cells.^47–51 Moreover, dietary patterns which modulate the gut microbiota have been shown to direct energy for either metabolic purposes or inflammation in intestinal cells, highlighting the critical balance between immune function and metabolism within intestinal epithelial cells.^52–54

It is therefore no wonder that aberrant microbiota profiles have been described for a range of metabolic and autoimmune diseases.^55,56 All of these appear to be impacted by diet, especially the polar opposites represented by low-fiber modern Western-style diets and high-fiber traditional diets based on whole plant foods from around the world, especially the Mediterranean diet, which has particularly strong evidence supporting its ability to protect against metabolic disease and cancer.^5,57–63 In the Western world, or in populations consuming the modern Western-style diet regardless of geographical location, incidences of both metabolic diseases (obesity, type 2 diabetes, cardiovascular disease, certain cancers and fatty liver disease) and autoimmune diseases (e.g., inflammatory bowel disease, type 1 diabetes, celiac disease, food allergies) are reaching epidemic-like numbers. In contrast, in populations following more traditional diets high in fiber and whole plant foods and low in processed, energy-dense food and red meat, these same diseases are rare.^64–66

Methodologies for Studying the Human Gut Microbiota

The vast majority of gut microorganisms remain uncultured or are difficult to culture under laboratory conditions. Early estimates indicated that at least 70% of microbial species within the gut microbiota were new to science and not isolated in pure culture or characterized in detail.⁶⁷ In fact, recent successes in cultivating strictly anaerobic and fastidious species like Faecalibacterium prausnitzii, a dominant and prevalent member of the gut microbiota, Roseburia spp. and Akkermansia muciniphila,^68,69 indicate that given appropriate nutrient availability, efficient selective agents to inhibit competing microorganisms and strict anaerobic cultivation conditions, it is probably true that most gut bacteria can be isolated in pure culture given enough patience.¹ In fact, one study recently indicated that cultured bacterial isolates are available for each of the most abundant 29 species, which represented 50% of the total gut microbial diversity.⁷⁰ Isolation in pure culture is important because it enables the physiology of a microorganism to be studied, allowing measurement of the phenotypic expression of its genetic blueprint under various growth conditions and in response to different environmental stressors. However, such studies are extremely time consuming and labor intensive, and it can take many years to fully characterize a given microbial strain. The high species richness of the gut microbiota, with perhaps 1000s of unique microbial strains, requires more direct techniques to measure both the genetic potential and metabolic kinetics of the gut microbiota as a whole. Different molecular strategies have been developed, aimed at addressing three fundamental ecological questions: which species/phylotypes are present? (their variability); how many of each are there? (their relative abundance); and what they are doing? (their metabolic activity). These different techniques each have their own advantages and disadvantages (for critical discussion of different molecular tools applied to microbial ecology, see references^71–73), and before embarking on a jour...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Foreword
• Acknowledgements
• List of Contributors
• Chapter 1. The Microbiota of the Human Gastrointestinal Tract: A Molecular View
• Chapter 2. A Nutritional Anthropology of the Human Gut Microbiota
• Chapter 3. Probiotic Microorganisms for Shaping the Human Gut Microbiota – Mechanisms and Efficacy into the Future
• Chapter 4. Bifidobacteria of the Human Gut: Our Special Friends
• Chapter 5. Shaping the Human Microbiome with Prebiotic Foods – Current Perspectives for Continued Development
• Chapter 6. Bioactivation of High-Molecular-Weight Polyphenols by the Gut Microbiome
• Chapter 7. Gut Microbial Metabolism of Plant Lignans: Influence on Human Health
• Chapter 8. Gut Microbiome Modulates Dietary Xenobiotic Toxicity: The Case of DON and Its Derivatives
• Chapter 9. Gut Microbiota–Immune System Crosstalk: Implications for Metabolic Disease
• Chapter 10. The Interplay of Epigenetics and Epidemiology in Autoimmune Diseases: Time for Geoepigenetics
• Chapter 11. Obesity-Associated Gut Microbiota: Characterization and Dietary Modulation
• Chapter 12. An Apple a Day Keeps the Doctor Away – Inter-Relationship Between Apple Consumption, the Gut Microbiota and Cardiometabolic Disease Risk Reduction
• Chapter 13. Whole Plant Foods and Colon Cancer Risk
• Chapter 14. Population Level Divergence from the Mediterranean Diet and the Risk of Cancer and Metabolic Disease
• Chapter 15. Diet and the Gut Microbiota – How the Gut: Brain Axis Impacts on Autism
• Index