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HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes

par Vandenbempt, Valerie ;Eski, Sema Elif ;Brahma, Manoja Kumar ;Li, Ao ;Negueruela Escudero, Javier ;Bruggeman, Ylke;Demine, Stéphane ;Xiao, Peng ;Cardozo, Alessandra K ;Baeyens, Nicolas ;Martelotto, Luciano;Singh, Sumeet Pal ;Mariño, Eliana;Gysemans, Conny;Gurzov, Esteban Nicolas
Référence iScience, 27, 1, page (108694)
Publication Publié, 2023-12-08

Article révisé par les pairs

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Résumé :

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 β-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 β-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.