HAMSAB modified gut microbiota signature in human type 1 diabetes delays disease after transfer into gnotobiotic mice

Progression to type 1 diabetes (T1D) is associated with a loss of fermentative gut bacteria that produce acetate and butyrate. In a recent trial, we administered a resistant starch prebiotic supplement that delivered acetate and butyrate in adults with T1D. Here, we demonstrate remodeling of the gut epithelium to promote repair pathways after the supplement. Multi-omics analysis found arginine and tryptophan metabolism correlated with markers of improved glycemic control. We used fecal microbiota transfer to demonstrate that the microbiota of supplement responder subjects delayed diabetes progression after colonization into mice. The protected mice increased butyrate, arginine and tryptophan metabolites along with downregulating B- and T-cell responses in the intestinal epithelium. Aryl-hydrocarbon receptor ligand production was increased in mice with slower diabetes progression. These data demonstrate that a dietary supplement in humans promotes a beneficial gut microbiota that can delay diabetes progression and support targeting the microbiota to prevent T1D.