Gut microbial metabolites alter IgA immunity in type 1 diabetes

The incidence of type 1 diabetes (T1D) has been increasing among children and adolescents, which environmental factors including gut microbiota play an important role. However, the underlying mechanisms are yet to be determined. Here, we show that patients with newly diagnosed T1D displayed not only a distinct profile of gut microbiota associated with decreased short-chain fatty acid (SCFAs) production, but also an altered IgA-mediated immunity compared with healthy control subjects. Using germ free (GF) non-obese diabetic (NOD) mice, we demonstrate that gut microbiota from patients with T1D promoted different IgA-mediated immune responses compared with healthy control gut microbiota. Treatment with the SCFA, acetate, reduced gut bacteria-induced IgA response accompanied by decreased severity of insulitis in NOD mice. Our study provides new insights into the functional effects of gut microbiota on inducing IgA immune response in T1D, suggesting that SCFAs might be potential therapeutic agents in T1D prevention and/or treatment