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
Affiliations
Valerie Vandenbempt
Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Sema Elif Eski
IRIBHM, Université libre de Bruxelles, 1070 Brussels, Belgium
Manoja K. Brahma
Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Ao Li
Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Javier Negueruela
Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Ylke Bruggeman
Clinical and Experimental Endocrinology (CEE), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), Campus Gasthuisberg O&N 1, KU Leuven, 3000 Leuven, Belgium
Stéphane Demine
Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Peng Xiao
Inflammatory and Cell Death Signaling in Diabetes group, Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Alessandra K. Cardozo
Inflammatory and Cell Death Signaling in Diabetes group, Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium
Nicolas Baeyens
Laboratoire de Physiologie et de Pharmacologie, Université Libre de Bruxelles, 1000 Brussels, Belgium
Luciano G. Martelotto
Single Cell and Spatial-Omics Laboratory, Adelaide Centre of Epigenetics, University of Adelaide, Adelaide, SA 5005, Australia
Sumeet Pal Singh
IRIBHM, Université libre de Bruxelles, 1070 Brussels, Belgium
Eliana Mariño
Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry, Monash University, Melbourne, VIC 3800, Australia; ImmunoBiota Therapeutics Pty Ltd, Melbourne, VIC 3187, Australia
Conny Gysemans
Clinical and Experimental Endocrinology (CEE), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), Campus Gasthuisberg O&N 1, KU Leuven, 3000 Leuven, Belgium
Esteban N. Gurzov
Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, 1070 Brussels, Belgium; WELBIO Department, WEL Research Institute, Avenue Pasteur 6, 1300 Wavre, Belgium; Corresponding author
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.
