Mouse gut metagenome. mouse gut metagenome

A gluten-free (GF) diet after weaning is known to decrease type 1 diabetes incidence in rodent models. As early life interventions in the intestinal environment have previously been shown to influence the diabetes incidence, we hypothesized that a GF diet only in the fetal and early postnatal life would protect against development of diabetes. Pregnant non-obese diabetic (NOD) mice were therefore fed a GF diet until they had given birth and the pups were weaned to a standard gluten-containing diet. The early gluten-free environment dramatically decreased diabetes incidence and gut microbiota analysis by pyro-sequencing revealed a vertically transferred shift in the offspring of gluten-free fed mice characterized by increased Akkermansia and Proteobacteria. In addition, pancreatic FoxP3 regulatory T cells and TGFβ were increased in GF fed NOD offspring at weaning, as were M2 macrophage gene markers in the gut, while intestinal gene expression of proinflammatory cytokines were reduced. It is possible that the mechanism involves increased trafficking of gut-primed immune cells to the pancreas; increased proportion of CD4 and CD8 T cells in the pancreas expressed the mucosal integrin α4β7 in the GF fed offspring. Thus, gluten-free diet during fetal and early postnatal life prevents diabetes in NOD mice. The mechanism may involve increased presence of Akkermansia and shifts to a less proinflammatory immunological millieu.