HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes

Valerie Vandenbempt; Sema Elif Eski; Manoja K Brahma; Ao Li; Javier Negueruela; Ylke Bruggeman; Stéphane Demine; Peng Xiao; Alessandra K Cardozo; Nicolas Baeyens; Luciano G Martelotto; Sumeet Pal Singh; Eliana Mariño; Conny Gysemans; Esteban N Gurzov

doi:10.1016/j.isci.2023.108694

HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes

iScience. 2023 Dec 10;27(1):108694. doi: 10.1016/j.isci.2023.108694. eCollection 2024 Jan 19.

Authors

Valerie Vandenbempt¹, Sema Elif Eski², Manoja K Brahma¹, Ao Li¹, Javier Negueruela¹, Ylke Bruggeman³, Stéphane Demine¹, Peng Xiao⁴, Alessandra K Cardozo⁴, Nicolas Baeyens⁵, Luciano G Martelotto⁶, Sumeet Pal Singh², Eliana Mariño^{7

8}, Conny Gysemans³, Esteban N Gurzov^{1

9}

Affiliations

¹ Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium.
² IRIBHM, Université libre de Bruxelles, 1070 Brussels, Belgium.
³ Clinical and Experimental Endocrinology (CEE), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), Campus Gasthuisberg O&N 1, KU Leuven, 3000 Leuven, Belgium.
⁴ Inflammatory and Cell Death Signaling in Diabetes group, Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium.
⁵ Laboratoire de Physiologie et de Pharmacologie, Université Libre de Bruxelles, 1000 Brussels, Belgium.
⁶ Single Cell and Spatial-Omics Laboratory, Adelaide Centre of Epigenetics, University of Adelaide, Adelaide, SA 5005, Australia.
⁷ Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry, Monash University, Melbourne, VIC 3800, Australia.
⁸ ImmunoBiota Therapeutics Pty Ltd, Melbourne, VIC 3187, Australia.
⁹ WELBIO Department, WEL Research Institute, Avenue Pasteur 6, 1300 Wavre, Belgium.

Abstract

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.

Keywords: Cell biology; Diabetology; Model organism; Transcriptomics.