Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation

Abstract

Background: Short chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria (dysbiosis), commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Currently, there are no microbiota-targeted interventions that investigate the imbalance of SCFAs in humans with T1D. Results: We conducted a single-arm pilot trial in adults with established T1D to determine the effects of dietary supplementation with high-amylose maize resistant starch modified by addition of acetate and butyrate (HAMSAB). SCFA concentrations were increased in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control. Bifidobacterium longum, Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention. Conclusion: Changes in gut microbiota composition, function and immune profile following six weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance and improve glycemic control for the treatment of T1D.