Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition, and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice

Abstract

β-Glucans (BGs), a group of complex dietary polysaccharides (CDPs), are available as dietary supplements. However, the effects of orally administered highly purified BGs on gut inflammation are largely unknown. The aim of this study was to investigate the impact of orally administering highly purified, yeast-derived BG (YBG; β-1,3/1,6-d-glucan) on susceptibility to colitis. Eight-week-old C57BL/6 (B6) mice were used in a series of experiments. Experiment (Expt) 1: male and female mice were treated every day, for 40 d, with saline (control) or 250 μg YBG, followed by 2.5% (wt:vol) dextran sulfate sodium (DSS) in drinking water during days 30-35; and colitis severity and intestinal immune phenotype were determined. Expt 2: female B6 mice were treated with saline or YBG for 30 d and intestinal immune phenotype, gut microbiota composition, and fecal SCFA concentrations were determined. Expt 3: female B6 mice were treated as in Expt 2, given drinking water with or without antibiotics [Abx; ampicillin (1g/L), vancomycin (0.5g/L), neomycin (1g/L), and metronidazole (1g/L)] during days 16-30, and gut immune phenotype and fecal SCFA concentrations were determined. Expt 4: female B6 Foxp3-green fluorescent protein (-GFP) reporter mice were treated as in Expt 3, and intestinal T-regulatory cell (Treg) frequencies and immune phenotypes were determined. Expt 5: female mice were treated as in Expt 1, given drinking water with or without antibiotics during days 16-40, and colitis severity and intestinal cytokine production were determined. Compared with controls, the YBG group in Expt 1 exhibited suppressive effects on features of colitis, such as loss of body weight (by 47%; P<0.001), shortening of colon (by 24%; P=0.016), and histopathology severity score (by 45%; P=0.01). The YBG group of Expt 2 showed a shift in the abundance of gut microbiota towards Bacteroides (by 16%; P=0.049) and Verrucomicrobia (mean±SD: control=7.8±0.44vs. YBG=21.0±9.6%) and a reduction in Firmicutes (by 66%; P<0.001). The YBG group also showed significantly higher concentrations of fecal SCFAs such as acetic (by 37%; P=0.016), propionic (by 47%; P=0.026), and butyric (by 57%; P=0.013) acids. Compared with controls, the YBG group of Expt 2 showed higher frequencies of Tregs (by 32%; P=0.043) in the gut mucosa. Depletion of gut microbiota in the YBG group of mice caused diminished fecal SCFA concentrations (Expt 3) and intestinal Treg frequencies (Expt 4). Compared with the YBG group, the YBG-(Abx) group of Expt 5 showed aggravated colitis features including loss of body weight (by >100%; P<0.01) and colonic inflammation score (by 42%; P=0.04). Studies using B6 mice show that dietary BGs are beneficial for promoting intestinal health when the gut microbiota is intact. However, these CDPs may produce adverse effects if gut microbiota is compromised.