Pretreatment with yeast derived complex dietary-polysaccharide leads to suppressed gut inflammation, altered microbiota composition and increased immune regulatory short-chain fatty acid production in C57BL/6 mice

ABSTRACT Background β-Glucans (BGs), a group of complex non-digestible polysaccharides, are considered to have beneficial health effects due to their immune modulatory properties and are considered as dietary supplements. However, the impact of oral administration of high-pure, well-defined BGs on gut inflammation, and the influence of intestinal microbiota and short-chain fatty acid (SCFA) on the therapeutic effect are largely unknown. Objectives The aim of this study, using a mouse model of chemical induced colitis, was to investigate the impact of oral administration of high-pure yeast BG (YBG) on the susceptibility to colitis, gut immune function, and structure and function of microbiota. Methods To determine the impact of oral administration of YBG on colitis susceptibility, eight week old C57BL/6 (B6) mice were pre-treated with YBG (250 μg/mouse/day) and given dextran sulfate sodium (DSS) in drinking water (2.5% w/v) and examined for the symptoms and features of colitis. To assess the effect of oral administration of YBG on gut mucosa and microbiota structure and function, and gut immune regulation, we determined the microbiota composition, fecal SCFA levels, and intestinal T cell phenotype and cytokine secretion. The role of gut microbiota in YBG treatment induced modulation of gut inflammation and immune function were determined in B6 mice treated with broad-spectrum antibiotic cocktail (1 g/L ampicillin, 0.5 g/L vancomycin, 1 g/L neomycin, and 1 g/L metronidazole) in drinking water. Results Compared to untreated mice, B6 mice that received prolonged pre-treatment with YBG showed diminished severity of different features of DSS-induced colitis including overall loss of body weight ( P <0.001), shortening of colon ( P =0.016) and histopathology ( P =0.01). However, high-pure YBG has no beneficial effect in terms of suppressing colitis severity when consumed only during the disease stage. Compared to untreated controls, YBG pre-treated mice showed higher regulatory T cell (Treg) frequencies ( P =0.043) in the gut mucosa, a shift in the abundance of gut microbiota towards polysaccharide-fermenting bacterial phyla Bacteroides ( P =0.049) and Verrucomicrobia (Mean±SD: control=13.0±0.33 vs YBG=10.9.7±0.69) and diminished Firmicutes ( P <0.001) and Proteobacteria ( P <0.001), and significantly higher production of SCFA such as acetic acid ( P =0.016), propionic acid ( P =0.026) and butyric acid ( P =0.013). Depletion of gut microbiota in YBG-fed B6 mice using broad spectrum antibiotics caused not only elimination of YBG treatment associated SCFA production and Treg increase, but also profound aggravation of the pathological features of colitis such as loss of body weight ( P <0.01) and colonic inflammation ( P =0.04) compared to that of YBG treated control mice. Conclusions Oral consumption of high-pure BG promotes a healthy gut homeostasis and immune regulation, and minimizes susceptibility to DSS induced colitis in B6 mice in a microbiota (and microbial SCFA) - dependent manner. On the contrary, YBG consumption when gut mucosa and microbiota are compromised not only reverses this protection but also increases the susceptibility to gut inflammation and disease severity, perhaps through its direct interaction with gut immune cells. In conclusion, while YBG consumption may be beneficial for gut health and to prevent gut inflammation in healthy individuals and under intact microbiota, this immune stimulatory dietary supplement may not have any health benefits in individuals with active gut inflammation and could cause adverse effect in those who are on oral antibiotics.