Yeast <i>β</i>-glucan supplementation lowers insulin resistance without altering microbiota composition compared with placebo in subjects with type II diabetes: a phase I exploratory study

The increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre 'Western diets'. Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast <i>β</i>-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinaemia and insulin resistance in a murine model. Here, we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition, while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2·5g/day of maltodextrin (placebo) or yeast <i>β</i>-1,3/1,6-D-glucan (treatment). Yeast <i>β</i>-glucan (Wellmune) lowered insulin resistance compared with the placebo maltodextrin after 8 weeks of consumption. TNF<i>α</i> was significantly lower after 4 weeks of <i>β</i>-glucan supplementation. Significantly higher fecal concentrations of several bile acids were detected in the treatment group when compared with the placebo after 8 weeks. These included tauroursodeoxycholic acid, which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast <i>β</i>-glucan was independent of any changes in fecal microbiota composition or short-chain fatty acid levels. Our findings highlight the potential of yeast <i>β</i>-glucan to lower insulin resistance in patients with T2DM.