Located in the mucus layer that lines the gastrointestinal tract, mucins-;proteins with attached sugar molecules-; play a key role in combating bacterial infection and providing a safe haven to friendly gut bacteria through unknown mechanisms. Although mucin dysregulation leads to metabolic disease and intestinal inflammation, the associated mechanism remains largely unknown. To address this knowledge gap, a team of researchers in Japan explored if the N-acetylglucosamine (GlcNAc)-6-O-sulfation of O-glycans, or the chemical modification of the sugar structures found in mucins, can help combat obesity and intestinal inflammation using a mouse model. This paper was made available online on August 22, 2023, and was published in Volume 8, Issue 16 of Journal of Clinical Investigation (JCI) Insight.
Initial experiments conducted by the team revealed a significant difference between the intestinal microbiota of regular or “wild type” (WT) mice and Chst4–/– mice that lacked the gene Chst4 for the GlcNAc-6-O-sulfation of mucin glycans. The latter developed obesity and showed vulnerability to both experimental colitis-;artificially induced inflammation of the colon-;and colitis-associated cancer.
Subsequent experiments revealed several key findings, a major among which was the following: Chst4–/– mice showed reduced fecal levels of immunoglobulin A (IgA), an antibody produced by the immune system that is essential for protecting mucosal surfaces, including the gut, against foreign invasions. Reduced IgA levels in the murine feces, thus, indicate a compromised immune system.
When asked about their results, Professor Hiroto Kawashima from Chiba University’s Graduate School of Pharmaceutical Science, the team’s lead researcher says, “Chst4–/– mice lacking