Gene-microbiota Interactions Contribute to the Pathogenesis of Inflammatory Bowel Disease

Overview

Journal Science

Specialty Science

Date 2016 May 28

PMID 27230380

Citations 294

Authors

Hiutung Chu

Arya Khosravi

Indah P Kusumawardhani

Alice H K Kwon

Anilton C Vasconcelos

Larissa D Cunha

Anne E Mayer

Yue Shen

Wei-Li Wu

Amal Kambal

Stephan R Targan

Ramnik J Xavier

Peter B Ernst

Douglas R Green

Dermot P B McGovern

Herbert W Virgin

Sarkis K Mazmanian

Affiliations

Soon will be listed here.

Abstract

Inflammatory bowel disease (IBD) is associated with risk variants in the human genome and dysbiosis of the gut microbiome, though unifying principles for these findings remain largely undescribed. The human commensal Bacteroides fragilis delivers immunomodulatory molecules to immune cells via secretion of outer membrane vesicles (OMVs). We reveal that OMVs require IBD-associated genes, ATG16L1 and NOD2, to activate a noncanonical autophagy pathway during protection from colitis. ATG16L1-deficient dendritic cells do not induce regulatory T cells (T(regs)) to suppress mucosal inflammation. Immune cells from human subjects with a major risk variant in ATG16L1 are defective in T(reg) responses to OMVs. We propose that polymorphisms in susceptibility genes promote disease through defects in "sensing" protective signals from the microbiome, defining a potentially critical gene-environment etiology for IBD.

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