Mucin-Derived O-Glycans Act as Endogenous Fiber and Sustain Mucosal Immune Homeostasis via Short-Chain Fatty Acid Production in Rat Cecum

J Nutr. 2020 Oct 12;150(10):2656-2665. doi: 10.1093/jn/nxaa097.

Abstract

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.

Keywords: N-acetylglucosamine; mucin-derived O-glycans; mucins; mucosal immune homeostasis; rats; short-chain fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cecum / drug effects
  • Dietary Fiber / administration & dosage*
  • Dietary Fiber / analysis
  • Dietary Fiber / pharmacology*
  • Fatty Acids, Volatile / metabolism*
  • Feces
  • Fermentation
  • Immunity, Mucosal / drug effects*
  • Mucins / chemistry
  • Mucins / metabolism*
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Dietary Fiber
  • Fatty Acids, Volatile
  • Mucins
  • Polysaccharides