Faecal mucoprotein MUC2 is decreased in multiple sclerosis and is associated with mucin degrading bacteria.

BACKGROUND: The gut microbiome is altered in MS and may contribute to disease by disrupting the intestinal barrier. The colonic mucus barrier, which is primarily composed of mucin protein 2 (MUC2), plays a crucial role in providing a barrier between colonic epithelial cells and the microbiome. Disruption of intestinal epithelial and mucus barriers has been reported in inflammatory bowel disease (IBD) and Parkinson's disease (PD) but has not been studied in the context of the microbiome in multiple sclerosis (MS). METHODS: We investigated the epithelial tight junction protein zonulin occludins 1 (ZO-1), mucus protein MUC2, inflammatory stool markers (calprotectin), and gut microbiota composition in a cohort of subjects with relapsing and progressive MS. FINDINGS: MUC2 was decreased in stool of subjects with both relapsing and progressive MS. ZO-1 was elevated in the serum of subjects with progressive MS but was not altered in the stool. Inflammatory markers typically elevated in IBD and PD, including calprotectin, were not altered in MS stool, suggesting disease specificity of altered gut physiology in MS. Microbiota with known mucus degrading capacity were elevated in the stool of subjects with MS and negatively correlated with mucus protein levels. INTERPRETATION: Taken together, these findings suggest reduced gut barrier function in MS which is linked to increased mucin degrading bacteria. FUNDING: This work was supported by grants from the National MS Society, the NIH/NINDS, the Nancy Davis Race to Erase MS Young Investigator Award, the Water Cove Charitable Foundation, and the Clara E. and John H. Ware Jr.