title: Altered mucus glycosylation in core 1 O-glycan-deficient mice affects microbiota composition and intestinal architecture.
abstract: A functional mucus layer is a key requirement for gastrointestinal health as it serves as a barrier against bacterial invasion and subsequent inflammation. Recent findings suggest that mucus composition may pose an important selection pressure on the gut microbiota and that altered mucus thickness or properties such as glycosylation lead to intestinal inflammation dependent on bacteria. Here we used TM-IEC C1galt (-/-) mice, which carry an inducible deficiency of core 1-derived O-glycans in intestinal epithelial cells, to investigate the effects of mucus glycosylation on susceptibility to intestinal inflammation, gut microbial ecology and host physiology. We found that TM-IEC C1galt (-/-) mice did not develop spontaneous colitis, but they were more susceptible to dextran sodium sulphate-induced colitis. Furthermore, loss of core 1-derived O-glycans induced inverse shifts in the abundance of the phyla Bacteroidetes and Firmicutes. We also found that mucus glycosylation impacts intestinal architecture as TM-IEC C1galt(-/-) mice had an elongated gastrointestinal tract with deeper ileal crypts, a small increase in the number of proliferative epithelial cells and thicker circular muscle layers in both the ileum and colon. Alterations in the length of the gastrointestinal tract were partly dependent on the microbiota. Thus, the mucus layer plays a role in the regulation of gut microbiota composition, balancing intestinal inflammation, and affects gut architecture.
authors.affiliation: The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden ; Mucin Biology Group, Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Felix
authors.initials: F
authors.lastname: Sommer
authors.affiliation: The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Adam
authors.affiliation: Mucin Biology Group, Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Malin E V
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.affiliation: Mucin Biology Group, Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
authors.affiliation: The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden ; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D016264:Dextran Sulfate; D005260:Female; D005693:Galactosemias / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D006031:Glycosylation; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D007422:Intestines / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology; D009093:Mucus / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D009929:Organ Size; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D016264:Dextran Sulfate