Host–microbiota interactions in inflammatory bowel disease

Abstract

The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. The presence of large numbers of symbionts near the epithelial surface of the intestine poses an enormous challenge to the host because it must avoid the activation of harmful inflammatory responses to the microorganisms while preserving its ability to mount robust immune responses to invading pathogens. In patients with inflammatory bowel disease, there is a breakdown of the multiple strategies that the immune system has evolved to promote the separation between symbiotic microorganisms and the intestinal epithelium and the effective killing of penetrant microorganisms, while suppressing the activation of inappropriate T cell responses to resident microorganisms. Understanding the complex interactions between intestinal microorganisms and the host may provide crucial insight into the pathogenesis of inflammatory bowel disease as well as new avenues to prevent and treat the disease.

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Fig. 1: Mucosal firewalls.
Fig. 2: Breakdown of mucosal firewalls in inflammatory bowel disease.
Fig. 3: Beneficial effects of symbionts.
Fig. 4: Regulatory T cells support intestinal homeostasis.
Fig. 5: Dysbiosis in inflammatory bowel disease.
Fig. 6: Effects of microbiome-based therapeutics in inflammatory bowel disease.

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Acknowledgements

The authors apologize to colleagues whose work was not cited or was cited through other review articles because of space limitations. The authors thank G. Chen for critical review of the manuscript. Work in G.N.’s laboratory is supported by US National Institutes of Health grants. R.C. is supported by a Career Developments Award from the Crohn’s and Colitis Foundation. B.C.L. is supported by a Canadian Institutes of Health Research (CIHR) Fellowship.

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Correspondence to Gabriel Núñez.

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Glossary

Pathobionts

Microorganisms that, under normal circumstances, live as non-harmful symbionts but can induce pathology under certain conditions, usually involving environmental and/or genetic alterations.

Crypts of Lieberkühn

Invaginations of the small intestine that contain epithelial stem cells and Paneth cells.

Oxidative burst

The rapid production of reactive oxygen species by phagocytes that can directly kill bacteria.

Segmented filamentous bacteria

(SFB). A species of Clostridium-related bacteria that primarily inhabits the terminal ileum of mice and promotes T helper 17 cell development.

Endoplasmic reticulum stress

A consequence of dysregulated protein processing in the endoplasmic reticulum that initiates unfolded protein response pathways; unresolved endoplasmic reticulum stress is associated with inflammatory bowel disease.

Unfolded protein response

(UPR). A group of intracellular signal transduction pathways that facilitates the folding, processing, export and degradation of proteins derived from the endoplasmic reticulum during stressed conditions.

Very early-onset IBD

A form of inflammatory bowel disease (IBD) diagnosed when symptoms manifest before the age of 6 years; it presents with a severe disease course, extensive colonic involvement, poor response to therapy and the frequent need for abdominal surgery.

Faecal stream diversion

A diverting terminal ileostomy constructed proximally to an ileocolonic anastomosis, thereby excluding the neoterminal ileum, the anastomosis and the colon from the faecal intestinal transit.

Tbx21 −/−Rag2 −/− mice

Immunocompromised mice that have no adaptive immune cells and only innate immune cells with a deficiency in T-box transcription factor 21 (TBX21).

16S ribosomal RNA gene sequencing

A DNA amplification technology for the study of a gene conserved among bacteria that is used for species identification and taxonomic classification of bacteria.

Adherent and invasive Escherichia coli

E. coli strains that can adhere to and invade intestinal epithelial cells.

Faecal microbiota transplantation

(FMT). The transfer of the intestinal microbial community from a healthy individual to a patient through infusion of stool, typically by endoscopy.

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Caruso, R., Lo, B.C. & Núñez, G. Host–microbiota interactions in inflammatory bowel disease. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-019-0268-7

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