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May 2014

Volume 146Issue 6p1433-1582
The Gut Microbiome in Health and Disease

Introduction

  • The Gut Microbiome in Health and Disease

    • Chung Owyang,
    • Gary D. Wu
    Published online: March 26, 2014
    p1433-1436
    Every May, Gastroenterology publishes a supplemental thirteenth issue devoted to a topic of particular interest and importance to both the practice and science of gastroenterology. The editorial board selected a series of reviews on the intestinal microbiome for this issue.

Basic Concepts in the Mammalian Gut Microbiome

  • Meta'omic Analytic Techniques for Studying the Intestinal Microbiome

    • Xochitl C. Morgan,
    • Curtis Huttenhower
    Published online: January 30, 2014
    p1437-1448.e1
    Nucleotide sequencing has become increasingly common and affordable, and is now a vital tool for studies of the human microbiome. Comprehensive microbial community surveys such as MetaHit and the Human Microbiome Project have described the composition and molecular functional profile of the healthy (normal) intestinal microbiome. This knowledge will increase our ability to analyze host and microbial DNA (genome) and RNA (transcriptome) sequences. Bioinformatic and statistical tools then can be used to identify dysbioses that might cause disease, and potential treatments.
    Online ExtraAdditional Online Content Available
  • Compositional and Functional Features of the Gastrointestinal Microbiome and Their Effects on Human Health

    • Emily B. Hollister,
    • Chunxu Gao,
    • James Versalovic
    Published online: January 31, 2014
    p1449-1458
    The human gastrointestinal tract contains distinct microbial communities that differ in composition and function based on their location, as well as age, sex, race/ethnicity, and diet of their host. We describe the bacterial taxa present in different locations of the GI tract, and their specific metabolic features. The distinct features of these specific microbial communities might affect human health and disease. Several bacterial taxa and metabolic modules (biochemical functions) have been associated with human health and the absence of disease.
  • Kingdom-Agnostic Metagenomics and the Importance of Complete Characterization of Enteric Microbial Communities

    • Jason M. Norman,
    • Scott A. Handley,
    • Herbert W. Virgin
    Published online: February 07, 2014
    p1459-1469
    Advanced sequencing techniques have shown that bacteria are not the only complex and important microbes in the human intestine. Nonbacterial organisms, particularly the virome and the mycobiome, are important regulators of intestinal immunity and inflammation. The virome is mucosal and systemic; it can alter the host response to bacteria and interact with host genes and bacteria to contribute to disease pathogenesis. The human mycobiome is also complex and can contribute to intestinal inflammation.
  • The Intestinal Metabolome: An Intersection Between Microbiota and Host

    • Luke K. Ursell,
    • Henry J. Haiser,
    • Will Van Treuren,
    • ...
    • Pieter C. Dorrestein,
    • Peter J. Turnbaugh,
    • Rob Knight
    Published online: March 13, 2014
    p1470-1476
    Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person’s physiological state based on their microbes and/or metabolites.
  • Regulation of the Immune System by the Resident Intestinal Bacteria

    • Nobuhiko Kamada,
    • Gabriel Núñez
    Published online: February 06, 2014
    p1477-1488
    The microbiota is an important factor in the development of the immune response. The interaction between the gastrointestinal tract and resident microbiota is well balanced in healthy individuals, but its breakdown can lead to intestinal and extraintestinal disease. We review current knowledge about the mechanisms that regulate the interaction between the immune system and the microbiota, focusing on the role of resident intestinal bacteria in the development of immune responses. We also discuss mechanisms that prevent immune responses against resident bacteria, and how the indigenous bacteria stimulate the immune system to protect against commensal pathobionts and exogenous pathogens.

The Gut Microbiome and Disease

  • The Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead

    • Aleksandar D. Kostic,
    • Ramnik J. Xavier,
    • Dirk Gevers
    Published online: February 21, 2014
    p1489-1499
    Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system.
  • Brain–Gut Microbiome Interactions and Functional Bowel Disorders

    • Emeran A. Mayer,
    • Tor Savidge,
    • Robert J. Shulman
    Published online: March 03, 2014
    p1500-1512
    Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics.
  • Interactions Between the Intestinal Microbiome and Liver Diseases

    • Bernd Schnabl,
    • David A. Brenner
    Published online: January 17, 2014
    p1513-1524
    The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to nonalcoholic fatty liver disease, steatohepatitis, alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes.
  • Role of the Microbiome in Energy Regulation and Metabolism

    • Max Nieuwdorp,
    • Pim W. Gilijamse,
    • Nikhil Pai,
    • Lee M. Kaplan
    Published online: February 21, 2014
    p1525-1533
    Intestinal microbes regulate metabolic function and energy balance; an altered microbial ecology is believed to contribute to the development of several metabolic diseases. Relative species abundance and metabolic characteristics of the intestinal microbiota change substantially in those who are obese or have other metabolic disorders and in response to ingested nutrients or therapeutic agents. The mechanisms through which the intestinal microbiota and its metabolites affect host homeostasis are just beginning to be understood.
  • Gastrointestinal Malignancy and the Microbiome

    • Maria T. Abreu,
    • Richard M. Peek Jr.
    Published online: January 08, 2014
    p1534-1546.e3
    Microbial species participate in the genesis of a substantial number of malignancies—in conservative estimates, at least 15% of all cancer cases are attributable to infectious agents. Little is known about the contribution of the gastrointestinal microbiome to the development of malignancies. Resident microbes can promote carcinogenesis by inducing inflammation, increasing cell proliferation, altering stem cell dynamics, and producing metabolites such as butyrate, which affect DNA integrity and immune regulation.
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  • Role of the Intestinal Microbiota in Resistance to Colonization by Clostridium difficile

    • Robert A. Britton,
    • Vincent B. Young
    Published online: February 06, 2014
    p1547-1553
    Antibiotic-associated infection with the bacterial pathogen Clostridium difficile is a major cause of morbidity and increased health care costs. C difficile infection follows disruption of the indigenous gut microbiota by antibiotics. Antibiotics create an environment within the intestine that promotes C difficile spore germination, vegetative growth, and toxin production, leading to epithelial damage and colitis. Studies of patients with C difficile infection and animal models have shown that the indigenous microbiota can inhibit expansion and persistence of C difficile.

Modification of the Gut Microbiome to Maintain Health or Treat Disease

  • Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies

    • Fergus Shanahan,
    • Eamonn M.M. Quigley
    Published online: January 30, 2014
    p1554-1563
    There is compelling rationale for manipulating the microbiota to treat inflammatory bowel diseases (IBDs). Although studies of animal models of intestinal inflammation produced promising results, trials in humans have been disappointing. In contrast to IBD, the role of the microbiota in the development of irritable bowel syndrome (IBS) only recently has been considered, but early stage results have been encouraging. As pharmaceutical companies develop fewer truly novel agents for treatment of these disorders, consumers seek safer, long-term strategies to deal with chronic symptoms.
  • Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease

    • Lindsey G. Albenberg,
    • Gary D. Wu
    Published online: February 06, 2014
    p1564-1572
    The mutual relationship between the intestinal microbiota and its mammalian host is influenced by diet. Consumption of various nutrients affects the structure of the microbial community and provides substrates for microbial metabolism. The microbiota can produce small molecules that are absorbed by the host and affect many important physiological processes. Age-dependent and societal differences in the intestinal microbiota could result from differences in diet. Examples include differences in the intestinal microbiota of breastfed vs formula-fed infants or differences in microbial richness in people who consume an agrarian plant-based vs a Western diet, which is high in meat and fat.
  • From Stool Transplants to Next-Generation Microbiota Therapeutics

    • Elaine O. Petrof,
    • Alexander Khoruts
    Published online: January 10, 2014
    p1573-1582
    The epidemic of Clostridium difficile infection fueled by new virulent strains of the organism has led to increased use of fecal microbiota transplantation (FMT). The procedure is effective for even the most desperate cases after failure of multiple courses of antibiotics. The approach recognizes microbiota to be integral to normal human physiology, and microbiota being used in FMT represents a new class of therapeutics. Imbalance in the composition and altered activity of the microbiota are associated with many diseases.

Frontmatter

  • Cover 1

    Published in issue: May 2014
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  • Editorial Board

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  • Table of Contents

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  • Information for Authors and Readers

    Published in issue: May 2014
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    Gastroenterology is the premiere journal in the field of gastrointestinal disease and is led by an internationally renowned board of editors. As the official journal of the AGA Institute, Gastroenterology delivers up-to-date and authoritative coverage of both basic and clinical gastroenterology and hepatology. Regular features include research and perspectives by leading authorities, reports on the latest technologies for diagnosing and treating digestive diseases, images illustrating important clinical findings, reviews of scholarly media, medical news, meeting summaries, video abstracts, and monthly podcasts.
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