Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection

• Published in: Cell reports (Cambridge) Vol. 42; no. 2; p. 112084
• Main Authors: Birchenough, George M.H., Schroeder, Bjoern O., Sharba, Sinan, Arike, Liisa, Recktenwald, Christian V., Puértolas-Balint, Fabiola, Subramani, Mahadevan V., Hansson, Karl T., Yilmaz, Bahtiyar, Lindén, Sara K., Bäckhed, Fredrik, Hansson, Gunnar C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28-02-2023; Elsevier
• Subjects: Cell and Molecular Biology; Cell Biology; Cell- och molekylärbiologi; Citrobacter rodentium; colonization resistance; CP: Immunology; CP: Microbiology; gut; host; jejunum; location; mucin; mucus; obesity; products; release; small intestine; tissue; western-style diet; CP: Immunology; CP: Microbiology; jejunum; western-style diet; small intestine; Citrobacter rodentium; colonization resistance; mucus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112084

Intestinal mucus barriers normally prevent microbial infections but are sensitive to diet-dependent changes in the luminal environment. Here we demonstrate that mice fed a Western-style diet (WSD) suffer regiospecific failure of the mucus barrier in the small intestinal jejunum caused by diet-induced mucus aggregation. Mucus barrier disruption due to either WSD exposure or chromosomal Muc2 deletion results in collapse of the commensal jejunal microbiota, which in turn sensitizes mice to atypical jejunal colonization by the enteric pathogen Citrobacter rodentium. We illustrate the jejunal mucus layer as a microbial habitat, and link the regiospecific mucus dependency of the microbiota to distinctive properties of the jejunal niche. Together, our data demonstrate a symbiotic mucus-microbiota relationship that normally prevents jejunal pathogen colonization, but is highly sensitive to disruption by exposure to a WSD.
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•Western-style diet disrupts the mucus layer in the small intestinal jejunum•The mucus layer is an essential habitat for the jejunal microbiota•Jejunal microbiota provides resistance against enteric pathogen colonization•Mucus supports colonization resistance by providing a niche for the microbiota
Birchenough et al. characterize regiospecific small intestinal mucus layer disruption after exposure to a Western-style diet. They show dependency of the jejunal microbiota on the presence of an intact mucus layer and demonstrate that mucus supports resistance against pathogen colonization by providing a habitat for the microbiota.