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Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043.

A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

Author information

1
Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette 4362, Luxembourg; University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg. Electronic address: mahesh.desai@lih.lu.
2
University of Michigan Medical School, Ann Arbor, MI 48109, USA.
3
Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg.
5
Aix-Marseille Université, UMR 7257, 13288 Marseille, France.
6
Department of Oncology, Luxembourg Institute of Health, Luxembourg 1526, Luxembourg.
7
Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette 4362, Luxembourg.
8
University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: emartens@umich.edu.

Abstract

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

KEYWORDS:

Akkermansia; Citrobacter rodentium; bacteroides; dietary fiber; gylcans; microbiome; microbiota; mucin; mucus layer; polysaccharides

PMID:
27863247
PMCID:
PMC5131798
DOI:
10.1016/j.cell.2016.10.043
[Indexed for MEDLINE]
Free PMC Article

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