January 2021

Volume 160Issue 2p479-624, e1
The Gut microbiome: Reaching the Promise through Discovery



  • The Gut Microbiome: Reaching the Promise Through Discovery— Advancing Knowledge and Discovery of the Gut Microbiome in the Age of Precision Medicine

    • Beth A. McCormick,
    • Eugene B. Chang
    Published online: December 28, 2020
    The gastrointestinal tract is home to nearly a trillion microbes that are comprised of bacteria, viruses, fungi, and other microorganisms which are collectively called the gut microbiome. Why have them, considering the potentially dire consequences of any entering the blood stream? As it turns out, we live in harmony with these microbes and they are of actual benefit to us, providing important cues for immunological, organismal, and metabolic development to name a few. However, are all gut microbes equal in this task or does this require teamwork by microbial communities and consortia? These queries beg the question of what is a “healthy” gut microbiome? As obvious as the answer might seem, one has not been found or agreed upon by general consensus.


  • The Healthy Microbiome—What Is the Definition of a Healthy Gut Microbiome?

    • Fergus Shanahan,
    • Tarini S. Ghosh,
    • Paul W. O’Toole
    Published online: November 26, 2020
    Use of microbiome-based biomarkers in diagnosis, prognosis, risk profiling, and precision therapy requires definition of a healthy microbiome in different populations. To determine features of the intestinal microbiota associated with health, however, we need improved microbiome profiling technologies, with strain-level resolution. We must also learn more about how the microbiome varies among apparently healthy people, how it changes with age, and the effects of diet, medications, ethnicity, geography, and lifestyle.
  • Childhood Development and the Microbiome—The Intestinal Microbiota in Maintenance of Health and Development of Disease During Childhood Development

    • Victoria Ronan,
    • Rummanu Yeasin,
    • Erika C. Claud
    Published online: December 07, 2020
    The composition of the intestinal microbiome affects health from the prenatal period throughout childhood, and many diseases have been associated with dysbiosis. The gut microbiome is constantly changing, from birth throughout adulthood, and several variables affect its development and content. Features of the intestinal microbiota can affect development of the brain, immune system, and lungs, as well as body growth. We review the development of the gut microbiome, proponents of dysbiosis, and interactions of the microbiota with other organs.
  • Aging, Frailty, and the Microbiome—How Dysbiosis Influences Human Aging and Disease

    • John P. Haran,
    • Beth A. McCormick
    Published online: December 07, 2020
    The human gut microbiome is a collection of bacteria, protozoa, fungi, and viruses that coexist in our bodies and are essential in protective, metabolic, and physiologic functions of human health. Gut dysbiosis has traditionally been linked to increased risk of infection, but imbalances within the intestinal microbial community structure that correlate with untoward inflammatory responses are increasingly recognized as being involved in disease processes that affect many organ systems in the body.
  • Inflammatory Bowel Diseases (IBD) and the Microbiome—Searching the Crime Scene for Clues

    • Mirae Lee,
    • Eugene B. Chang
    Published online: November 26, 2020
    Inflammatory bowel diseases (IBD) develop via convergence of environmental, microbial, immunological, and genetic factors. Alterations in the gut microbiota have been associated with development and progression of IBD, but it is not clear which populations of microbes are involved or how they might contribute to IBD. We review the genetic and environmental factors affecting the gut microbiota, the roles of gut microbes and their bioproducts in the development and clinical course of IBD, and strategies by which microbiome-based therapies can be used to prevent, manage, and eventually cure IBD.
  • Functional Gastrointestinal Disorders and the Microbiome—What Is the Best Strategy for Moving Microbiome-based Therapies for Functional Gastrointestinal Disorders into the Clinic?

    • Ruben A.T. Mars,
    • Mary Frith,
    • Purna C. Kashyap
    Published online: November 27, 2020
    There have been numerous human studies reporting associations between the intestinal microbiome and functional gastrointestinal disorders (FGIDs), and independently animal studies have explored microbiome-driven mechanisms underlying FGIDs. However, there is often a disconnect between human and animal studies, which hampers translation of microbiome findings to the clinic. Changes in the microbiota composition of patients with FGIDs are generally subtle, whereas changes in microbial function, reflected in the fecal metabolome, appear to be more precise indicators of disease subtype-specific mechanisms.
  • Chronic Liver Diseases and the Microbiome—Translating Our Knowledge of Gut Microbiota to Management of Chronic Liver Disease

    • Chathur Acharya,
    • Jasmohan S. Bajaj
    Published online: November 27, 2020
    Chronic liver disease is reaching epidemic proportions with the increasing prevalence of obesity, nonalcoholic liver disease, and alcohol overuse worldwide. Most patients are not candidates for liver transplantation even if they have end-stage liver disease. There is growing evidence of a gut microbial basis for many liver diseases, therefore, better diagnostic, prognostic, and therapeutic approaches based on knowledge of gut microbiota are needed. We review the questions that need to be answered to successfully translate our knowledge of the intestinal microbiome and the changes associated with liver disease into practice.
  • Metabolism and Metabolic Disorders and the Microbiome: The Intestinal Microbiota Associated With Obesity, Lipid Metabolism, and Metabolic Health—Pathophysiology and Therapeutic Strategies

    • Judith Aron-Wisnewsky,
    • Moritz V. Warmbrunn,
    • Max Nieuwdorp,
    • Karine Clément
    Published online: November 26, 2020
    Changes in the intestinal microbiome have been associated with obesity and type 2 diabetes, in epidemiological studies and studies of the effects of fecal transfer in germ-free mice. We review the mechanisms by which alterations in the intestinal microbiome contribute to development of metabolic diseases, and recent advances, such as the effects of the microbiome on lipid metabolism. Strategies have been developed to modify the intestinal microbiome and reverse metabolic alterations, which might be used as therapies.
  • Cancer and the Microbiome—Influence of the Commensal Microbiota on Cancer, Immune Responses, and Immunotherapy

    • Vyara Matson,
    • Carolina Soto Chervin,
    • Thomas F. Gajewski
    Published online: November 27, 2020
    The commensal microbiota has been implicated in the regulation of a diverse array of physiological processes, both within the gastrointestinal tract and at distant tissue sites. Cancer is no exception, and distinct aspects of the microbiota have been reported to have either pro- or anti-tumor effects. The functional role of the microbiota in regulating not only mucosal but also systemic immune responses has led to investigations into the impact on cancer immunotherapies, particularly with agents targeting the immunologic checkpoints PD-1 and CTLA-4.
  • Probiotics and the Microbiome—How Can We Help Patients Make Sense of Probiotics?

    • Robert A. Britton,
    • Diane E. Hoffmann,
    • Alexander Khoruts
    Published online: December 08, 2020
    The notion of probiotics as microbes that confer health benefits has its origins in the speculative ideas that are more than a century old, yet remain largely unsubstantiated by scientific evidence. The recent advances in microbiome science have highlighted the importance of intestinal microbes in human physiology and disease pathogenesis. These developments have provided a boost to the probiotics industry, which continues to experience exponential growth driven mainly by creative marketing. Consumers, patients, and most health care providers are not able to discern the underlying science or differentiate the permitted claims that promise vague health benefits from disease-specific claims reserved for drugs.


  • Cover 1

    Published in issue: January 2021
  • Editorial Board

    Published in issue: January 2021
  • Table of Contents

    Published in issue: January 2021
  • Elsewhere in The AGA Journals

    Published in issue: January 2021
  • Information for Authors and Readers

    Published in issue: January 2021
    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.