ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Gut microbiota targeted dietary supplements as a potential therapy for type 1 diabetes (#210)

Kirstine J Bell 1 , Sonia Saad 2 , Bree J Tillett 3 , Helen M McGuire 1 , Yu Anne Yap 4 , Barbara Fazekas de St Groth 1 , Charles Mackay 4 , Esteban N Gurzov 5 , Eliana Marino 4 , Emma E Hamilton-Williams 3
  1. Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
  2. Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
  3. University of Queensland Diamantina Institute, Brisbane, QLD
  4. Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia
  5. Signal Transduction and Metabolism Laboratory, Université libre de Bruxelles, Brussels, Belgium

Multiple studies have linked changes in the composition or function of the gut microbiota with type 1 diabetes (T1D). A reduction in genes or taxa able to ferment fibre into short-chain fatty acids (SCFA) is proposed to be one of the most consistently identified functional changes in the T1D gut microbiota. These microbially produced SCFA are known to promote intestinal barrier function and immune tolerance and can prevent T1D in rodent models. SCFA also have beneficial effects on glucose metabolism. Therapeutic strategies that restore microbial SCFA production therefore hold promise for restoration of immune tolerance and prevention or treatment of T1D. In this study, we conducted a single-armed pilot study of a diet-based therapy targeting the gut microbiota in 21 adults with established T1D. Participants consumed a dietary supplement consisting of acetylated and butyrylated modified resistant starch, which is fermented in the colon to release the SCFA acetate and butyrate, for 6 weeks. We show that substantial changes in the composition and function of the gut microbiota and increased stool and plasma acetate and butyrate concentrations followed dietary supplementation. Mass cytometry analysis of PBMCs found that antigen-presenting cells reduced CD86 costimulatory molecule expression while T cells increased regulatory markers CTLA4 and TIGIT following the diet. While glycaemic variables such as HbA1c and basal insulin did not significantly change from baseline, serum HbA1c and basal insulin were both significantly negatively correlated with plasma butyrate concentration over the course of the study. These data support further investigation into delivery of SCFA for the treatment or prevention of type 1 diabetes.