HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes

An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously demonstrated that enhancing serum acetate and butyrate using a dietary supplement (HAMSAB) improved glycemia in non-obese diabetic (NOD) mice and patients with established T1D. The effects of SCFA on immune-infiltrated islet cells remain to be clarified. Here, we performed single-cell RNA sequencing on islet cells from NOD mice fed an HAMSAB or control diet. HAMSAB induced a regulatory gene expression profile in pancreas-infiltrated immune cells. Moreover, HAMSAB maintained the expression of b-cell functional genes and decreased cellular stress. HAMSAB-fed mice showed preserved pancreatic endocrine cell identity, evaluated by decreased numbers of poly-hormonal cells. Finally, SCFA increased insulin levels in human b-like cells and improved transplantation outcome in NOD/SCID mice. Our findings support the use of metabolite-based diet as attractive approach to improve glucose control in T1D.Valerie Vandenbempt, Sema Elif Eski, Manoja K. Brahma, Ao Li, Javier Negueruela, Ylke Bruggeman, Stephane Demine, Peng Xiao, Alessandra K. Cardozo, Nicolas Baeyens, Luciano G. Martelotto, Sumeet Pal Singh, Eliana Marin, o, Conny Gysemans, and Esteban N. Gurzo