Open AccessMucin-Derived O-Glycans Act as Endogenous Fiber and Sustain Mucosal Immune Homeostasis via Short-Chain Fatty Acid Production in Rat Cecum
Author(s) -
Shingo Hino,
Takayasu Mizushima,
Katsunori Kaneko,
Erika Kawai,
Takashi Kondo,
Tomomi Genda,
Takahiro Yamada,
Koji Hase,
Naomichi Nishimura,
Tatsuya Morita
Publication year - 2020
Publication title -
the journal of nutrition/the journal of nutrition
Language(s) - English
Resource type - Journals
eISSN - 1541-6100
pISSN - 0022-3166
DOI - 10.1093/jn/nxaa097
Subject(s) - mucin , cecum , butyrate , mucin 2 , ileum , glycan , biology , fucose , immune system , biochemistry , endocrinology , medicine , chemistry , immunology , fermentation , glycoprotein , gene expression , gene
Background Intestinal mucins escape digestion and enter the large bowel where they are degraded by the microbiota. To what extent and how mucins impact large-bowel physiology remain unclear. Objective This study examined the large-bowel fermentation characteristics of mucins and mucin-derived O-glycan sugars and whether they affect gut immunity. Methods Mucin secretion from the terminal ileum was determined from feces of ileorectostomized male Wistar rats (age 6 wk) fed an AIN76-based control diet (CD) for 15 d (experiment 1). Normal male Wistar rats (age 6 wk; 4 wk for experiment 4) were fed CD ± porcine stomach mucin (PM) at 6 or 12 g/kg diet, equivalent to 1.5 and 3 times the daily mucin secretion, for 14 d (experiment 2); CD ± N-acetylglucosamine (GlcNAc), fucose, or N-acetylneuraminic acid at 10 g/kg diet for 14 d (experiment 3); or CD ± PM (15 g/kg diet) or GlcNAc (10 g/kg diet) for 29 d (experiment 4). SCFAs, microbial composition, and cecal O-glycan content were assessed. IgA+ plasma cells and regulatory T cells and inflammatory cytokine expression in the cecum were evaluated (experiment 4). Results Daily mucin secretion corresponded to 43.2 μmol of O-glycans. Cecal O-glycan contents were comparable between CD- and PM-fed rats. PM-fed rats harbored more mucin-degrading bacteria. Cecal concentrations of acetate (+37%) and n-butyrate (+73%) were higher in 12-g/kg PM diet–fed rats versus CD (P < 0.05). Among O-glycan sugars, only GlcNAc produced higher n-butyrate concentrations (+68%) versus CD (P < 0.05), with increased numbers of butyrate-producing bacteria. GlcNAc increased the abundance of IgA+ plasma cells (+29%) and regulatory T cells (+33%) versus CD, whereas PM increased IgA+ plasma cells (+25%) (all P < 0.05). GlcNAc and PM decreased expression of Tnfa (−30%, −40%) and Ifng (−30%, −70%) versus CD (all P < 0.05). Conclusions Mucin-derived O-glycans act as endogenous fiber and maintain mucosal immune homeostasis via large-bowel SCFA production in rats.