Dietary HAMSAB supplementation enhances SCFA production associated with microbiota and immune modulation in type 1 diabetes. HAMSAB clinical T1D trial

Short chain fatty acids (SCFAs) produced by the gut microbiota have dual beneficial anti inflammatory and anti-dysbiotic effects associated with the prevention of type 1 diabetes (T1D) in mice. We conducted a single-arm human trial to determine the effects of dietary supplementation with acetate and butyrate (HAMSAB) in adults with long-standing T1D. SCFA concentrations were significantly increased in the stool and circulation in concert with a shift in the composition and function of the gut microbiota. Subjects with the highest concentrations of SCFAs exhibited better glycaemic control. Bifidobacterium longum andBifidobacterium adolescentis and vitamin B7 production correlated with lower HbA1c and/or lower basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention. This novel microbiota-targeted approach increased SCFAs, restored beneficial gut microbiota, and modulated the immune system. Persistence of these effects suggests that HAMSAB supplementation may have therapeutic benefit to promote immune tolerance to beta-cell antigens and improve glycemic control for the prevention or treatment of T1D.