Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection
George M.H. Birchenough,
Bjoern O. Schroeder,
Sinan Sharba,
Liisa Arike,
Christian V. Recktenwald,
Fabiola Puértolas-Balint,
Mahadevan V. Subramani,
Karl T. Hansson,
Bahtiyar Yilmaz,
Sara K. Lindén,
Fredrik Bäckhed,
Gunnar C. Hansson
Affiliations
George M.H. Birchenough
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular & Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Corresponding author
Bjoern O. Schroeder
Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Sinan Sharba
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Liisa Arike
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Christian V. Recktenwald
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Fabiola Puértolas-Balint
Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden
Mahadevan V. Subramani
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular & Translational Medicine, University of Gothenburg, Gothenburg, Sweden
Karl T. Hansson
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular & Translational Medicine, University of Gothenburg, Gothenburg, Sweden
Bahtiyar Yilmaz
Department for BioMedical Research, University of Bern, Bern, Switzerland
Sara K. Lindén
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Fredrik Bäckhed
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Gunnar C. Hansson
Department of Medical Biochemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Summary: 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.
