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Environmental triggers in IBD: a review of progress and evidence

Key Points

  • Gut microbiota composition is known to be important in maintaining health and mediating disease

  • Dysbiosis, a change in the normal microbial ecology, occurs in the intestine in the context of IBD

  • Gut inflammation in IBD is characterized by a reduced diversity of microbiota, which could render the host more susceptible to colonization with pathogens or pathobionts

  • Environmental factors probably have a major role in IBD; antibiotic use, childbirth mode, breastfeeding, air pollution, NSAID use, hypoxia or high altitude, diet and urban environments have been studied

  • Future studies should adopt a multi-omic big data approach, integrating several layers of data on clinical parameters, environmental exposures, genetics, epigenetics, immunological function and microbial structure

Abstract

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

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Figure 1: Environmental factors contributing to IBD pathogenesis.
Figure 2: Lifelong influences on the gut microbiome from conception to adult life lead to dysbiosis and development of IBD.
Figure 3: IBD — a continuously evolving biological process.

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A.N.A. and C.F. drafted the manuscript. All authors made critical revisions of the manuscript for content and figures, and edited the manuscript.

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Correspondence to Ashwin N. Ananthakrishnan.

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Competing interests

A.N.A. has served on advisory boards for AbbVie, Merck and Takeda. C.N.B. is supported in part by the Bingham Chair in Gastroenterology. He has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Napo Pharmaceuticals, Pfizer Canada, Shire Canada and Takeda Canada, and he has acted as a consultant to Mylan Pharmaceuticals. He has received educational grants from AbbVie Canada, Janssen Canada, Shire Canada and Takeda Canada. He has been on the speaker's panel for AbbVie Canada, Ferring Canada and Shire Canada. The other authors declare no competing interests.

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iCluster

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Glossary

IBD

Two diseases (Crohn's disease and ulcerative colitis) affecting primarily the digestive tract, characterized by chronic inflammation.

Microbiota

Community of microorganisms comprising bacteria, viruses, fungi, Archaea and eukaryotic microorganisms.

Xenobiotics

Substances that are foreign to the body.

Pathobionts

Microorganisms associated with chronic inflammatory diseases.

Archaea

A kingdom of single-cell microorganisms without a nucleus or membrane-bound organelles.

Hypoxia

A state of reduced oxygenation in the tissues.

Exposome

The entirety of all environmental exposures of an individual in a lifetime.

Epigenome

DNA methylation and histone modifications that regulate expression of genes within a cell.

Metabolomics

Study of chemical fingerprints (metabolites) present within an organism.

Phenomics

Measurement of physical and biochemical traits of an organism.

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Ananthakrishnan, A., Bernstein, C., Iliopoulos, D. et al. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol 15, 39–49 (2018). https://doi.org/10.1038/nrgastro.2017.136

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