HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes
Summary
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. © 2023 The Author(s).
Authors | Vandenbempt V, Eski SE, Brahma MK, Li A, Negueruela J, Bruggeman Y, Demine S, Xiao P, Cardozo AK, Baeyens N, Martelotto LG, Singh SP, Mariño E, Gysemans C, Gurzov EN |
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Journal | iScience |
Publication Date | 2024 Jan 19;27(1):108694 |
PubMed | 38213620 |
PubMed Central | PMC10783594 |
DOI | 10.1016/j.isci.2023.108694 |