LAUSR

Intestinal mucins escape digestion and enter the large bowel where they are degraded by microbiome. To what extent and how mucins impact large-bowel physiology remain unclear. This study examined the large-bowel fermentation characteristics of mucins and mucin-derived O-glycan sugars and whether mucins and N-acetylglucosamine (GlcNAc) affect gut immunity. Mucin secretion from the terminal ileum was determined from feces of ileorectostomized male Wistar rats (age 6 weeks) fed AIN76-based control diet (CD) for 15 d (Expt. 1). Normal male Wistar rats (age 6 weeks; 4 weeks for Expt. 4) were fed CD ± porcine stomach mucin (PM) at 6 or 12g/kg diet, equivalent to 1.5 and 3 times daily mucin secretion, for 14 d (Expt. 2); CD ± GlcNAc, fucose, or N-acetylneuraminic acid at 10g/kg diet for 14 d (Expt. 3); or CD ± PM (15 g/kg diet) or GlcNAc (10 g/kg diet) for 29 d (Expt. 4). Short-chain fatty acids (SCFAs), microbial composition, and cecal O-glycan content were assessed. IgA+ plasma and regulatory T cells and inflammatory cytokine expression in the cecum were evaluated (Expt. 4). Daily mucin secretion corresponded to 43.2 mmol of O-glycans. PM was efficiently fermented in the cecum, as evidenced by comparable amounts of cecal O-glycans between groups. PM-fed rats harbored more mucin-degrading bacteria. Cecal SCFA concentrations, particularly n-butyrate, were higher in 12g/kg PM diet-fed rats versus CD (P < 0.05). Among O-glycan sugars, only GlcNAc produced higher n-butyrate concentrations versus CD (P < 0.05), with increased numbers of several butyrate-producing bacteria. GlcNAc increased the abundance of IgA + plasma and regulatory T cells versus CD (P < 0.05). PM produced a similar but less-significant trend. GlcNAc and PM feeding decreased expression of Tnfa and Ifng versus CD (P < 0.05). Mucin-derived O-glycans act as endogenous fiber and maintain mucosal immune homeostasis via large-bowel SCFA production in rats. JSPS KAKENHI.