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Gut microbiota and IBD: causation or correlation?

Key Points

  • Alterations in intestinal microbial composition have long been associated with chronic inflammation; however, a definitive cause–effect relationship between dysbiosis and IBD has been difficult to prove, especially in humans

  • Dysbiosis alters not only the composition of the intestinal microbiota, but also its metabolome, thereby exerting a wide range of effects on the host

  • While the microbiota plays a key pathogenic role in IBD, chronic inflammation, in turn, promotes dysbiosis by altering the oxidative and metabolic environment of the gut

  • Animal studies have elucidated key immunological pathways in the pathogenesis of IBD, established both pro-inflammatory and anti-inflammatory roles of the gut microbiota, and shown that the gut microbiota is indispensable for pathogenesis in most colitis models

  • Microbial-based treatments will likely have a role in the future management of IBD; however, many questions remain regarding the bacterial composition, timing of administration, and patient selection for such therapies

Abstract

A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host–microbial relationships relevant to human disease and amenable to therapeutic interventions.

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Figure 1: Colonic inflammation in IBD and link to the gut microbiota.
Figure 2: Pro-inflammatory and anti-inflammatory effects of the gut microbiota.

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Acknowledgements

J.N. acknowledges support from the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007066-40) and holds the AGA-Takeda Pharmaceuticals Research Scholar Award in Inflammatory Bowel Disease. G.D.W. acknowledges funding from PennCHOP Microbiome Program, NIH grants R01 DK107565, R24 AI 118629, and the Crohn's and Colitis Foundation Microbiome Initiative. L.A. acknowledges support from grant K23DK109136-01. V.T.T. acknowledges support from NIH grant K08-DK097301.

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Correspondence to Vesselin T. Tomov.

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Seres Therapeutics has an option agreement with the University of Pennsylvania for some intellectual property, listing G.D.W. as an inventor.

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Glossary

Crohn's disease

A chronic inflammatory bowel disease that can involve the entire gastrointestinal tract and is characterized by areas of transmural inflammation surrounded by normal mucosa.

Ulcerative colitis

A chronic inflammatory bowel disease characterized by diffuse mucosal inflammation limited to the colon.

Dysbiosis

An alteration of the microbiota that is associated with disease.

Faecal diversion

Surgical diversion of the faecal stream by means of a loop ileostomy or colostomy.

Virome

The collection of prokaryotic and eukaryotic viruses that are part of the human microbiota.

Bacteriophages

Viruses that infect and replicate within bacteria.

Bile acids

Steroid acids found in bile that aid in fat emulsification and nutrient digestion.

Short-chain fatty acids

Fatty acids with less than 6 carbons produced by bacterial fermentation of dietary carbohydrates.

Immunoglobulin A

(IgA). The most abundant antibody type, mostly associated with mucosal surfaces.

Ileocolonic resection

Resection of the terminal ileum, caecum and ascending colon, followed by an ileocolonic anastomosis.

Ileostomy

A surgical operation in which a piece of the ileum is diverted to an artificial opening in the abdominal wall.

Probiotics

Living microorganisms which, when administered in adequate amounts, might confer health benefits on the host.

Enteral nutritional therapy

(ENT). Nutritional supplementation via a nasoenteric feeding tube.

Faecal microbiota transplantation

(FMT). The administration of microorganisms derived from the stool of a healthy donor to the gastrointestinal tract of a patient.

Coprophagia

The consumption of faeces.

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Ni, J., Wu, G., Albenberg, L. et al. Gut microbiota and IBD: causation or correlation?. Nat Rev Gastroenterol Hepatol 14, 573–584 (2017). https://doi.org/10.1038/nrgastro.2017.88

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