biostudies-literatureAbo HTakeda Medical Research FoundationMizutani Foundation for GlycoscienceJapan Agency for Medical Research and DevelopmentJapan Foundation for Applied EnzymologyMochida Memorial Foundation for Medical and Pharmaceutical ResearchJapan Society for the Promotion of Sciencee165944https://www.ebi.ac.uk/biostudies/studies/S-EPMC10543739biostudies-literatureUnknown8(16)Intestinal mucins play an essential role in the defense against bacterial invasion and the maintenance of gut microbiota, which is instrumental in the regulation of host immune systems; hence, its dysregulation is a hallmark of metabolic disease and intestinal inflammation. However, the mechanism by which intestinal mucins control the gut microbiota as well as disease phenotypes remains nebulous. Herein, we report that N-acetylglucosamine (GlcNAc)-6-O sulfation of O-glycans on intestinal mucins performs a protective role against obesity and intestinal inflammation. Chst4-/- mice, lacking GlcNAc-6-O sulfation of the mucin O-glycans, showed significant weight gain and increased susceptibility to dextran sodium sulfate-induced colitis as well as colitis-associated cancer accompanied by signifJCI insightN-acetylglucosamine-6-O sulfation on intestinal mucins prevents obesity and intestinal inflammation by regulating gut microbiota.PMC1054373918K1512820ae0101034h0005No number20H0337920K1598618K06505Muraki AAbo HSuzuki MKawashima HHarusato AImura TTakahashi KDenning TLfalseN-acetylglucosamine-6-O sulfation on intestinal mucins prevents obesity and intestinal inflammation by regulating gut microbiota.Intestinal mucins play an essential role in the defense against bacterial invasion and the maintenance of gut microbiota, which is instrumental in the regulation of host immune systems; hence, its dysregulation is a hallmark of metabolic disease and intestinal inflammation. However, the mechanism by which intestinal mucins control the gut microbiota as well as disease phenotypes remains nebulous. Herein, we report that N-acetylglucosamine (GlcNAc)-6-O sulfation of O-glycans on intestinal mucins performs a protective role against obesity and intestinal inflammation. Chst4-/- mice, lacking GlcNAc-6-O sulfation of the mucin O-glycans, showed significant weight gain and increased susceptibility to dextran sodium sulfate-induced colitis as well as colitis-associated cancer accompanied by signif2023-01-01T00:00:00Z2023 Aug2026-05-29T01:47:08.159Z2025-04-19T23:53:27.329ZS-EPMC105437393746305510.1172/jci.insight.165944