Gastroenterology

Gastroenterology

Volume 146, Issue 6, May 2014, Pages 1500-1512
Gastroenterology

The Gut Microbiome and Disease
Brain–Gut Microbiome Interactions and Functional Bowel Disorders

https://doi.org/10.1053/j.gastro.2014.02.037Get rights and content

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. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut–brain interactions.

Section snippets

Alterations in the Intestinal Microbiome of Patients With IBS

Advances in analytic techniques have helped to better characterize different aspects of the gut microbiome.22, 23, 24 Only 20%–30% of microbes identified in the human colon can be cultured (mostly Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria); these new techniques can be used to assess diversity and functional groups.12 Culture-independent approaches include 16S ribosomal RNA gene-based analyses (to identify microbes in the GI tract), metagenomic approaches (to determine which

Possible Causes of Dysbiosis in Patients With IBS

A small percentage of patients (8%–15%) have persistent IBS-like symptoms after an initial documented episode of enteric bacterial or viral infection, called postinfectious IBS. This observation supports a role for a perturbed intestinal microbiome in the development of altered brain–gut interactions associated with IBS-like symptoms. Common bacterial causes of traveler’s diarrhea (Escherichia coli, Salmonella, and Campylobacter) strongly are associated with postinfectious IBS, and biological

The Intestinal Microbiota and the Central Nervous System

The central nervous system (CNS) modulates the GI tract via the sympathetic and parasympathetic branches of the ANS and the HPA axis. These can affect the enteric microbiota indirectly by altering its environment, and directly via signaling molecules (reviewed by Rhee et al2). Both branches of the ANS regulate gut functions such as regional motility, secretion of acid, production of bicarbonates and mucus, maintenance of epithelial fluid, permeability of the intestine, and the mucosal immune

Gut Microbiota Modulate Gut–Brain Interactions

There are multiple ways, levels, and signaling mechanisms by which the microbiota can influence interactions between the gut and the nervous system, including the brain. Such influences may occur early in life and affect the development of the nervous system, the brain’s interaction with the intestine, and the HPA axis, or in adults act on fully developed circuits (reviewed by Forsythe and Kunze,5 Cryan and Dinan,8 and Bercik et al9). There have been more review articles and news stories on

Future Directions

There have been many exciting studies providing new insights into the complex interactions between the microbiota, intestinal cells, the ENS, and the CNS, but little is known about their role in the development of IBS or the maintenance of IBS symptoms. Studies in rodents and healthy individuals have provided evidence that the intestinal microbiota can be modulated by the ANS, and possibly by the HPA axis. On the other hand, other preclinical studies, and a recent clinical study,20 have shown

Acknowledgment

The authors thank Dr J. Versalovic for valuable scientific advice and C. Liu for invaluable editorial assistance.

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    Conflicts of interest The authors disclose the following: Dr Emeran A. Mayer is a member of the International Danone Advisory Board. The remaining authors disclose no conflicts.

    Funding Supported in part by National Institutes of Health grants DK 64531 (E.A.M.), DK 48351 (E.A.M.), NINR 5337 (R.J.S.), NINR 13497 (R.J.S.), AI100914 (T.S.), and DK56338 (T.S.).

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