Butyrate Ameliorates Antibiotic-Driven Type 1 Diabetes in the Female Offspring of Nonobese Diabetic Mice

Maternal gut dysbiosis affects the development of the offspring immune system. Our previous study has indicated that microbial metabolite butyrate directly shapes pancreatic immune tolerance and dampens type 1 diabetes (T1D) progression. Therefore, maternal butyrate intervention may protect their offspring from maternal gut dysbiosis-accelerated T1D. To test this, pregnant nonobese diabetic (NOD) mice were treated with vancomycin in drinking water with or without a butyrate-supplemented diet during gestation and nursing (oral vancomycin is used to induce maternal gut dysbiosis). Three weeks after delivery, T1D-associated innate and adaptive immune cells were detected to investigate the effects of butyrate on the vancomycin-exacerbated pancreatic immune disorder in dams and pups. The results showed that butyrate inhibited maternal vancomycin-exacerbated secretion of proinflammation cytokines (interferon γ and interleukin-1β) and maternal vancomycin-exacerbated recruitment of interferon γ+ T cells (cytotoxic T lymphocytes 1 cells and T helper type 1 cells) in the pancreas of the female offspring, thus dampening T1D development. The protection may be due to butyrate inhibiting the activation of pancreatic dendritic cells (DCs). Our data thus demonstrate that maternal gut dysbiosis can exacerbate pancreatic-directed autoimmunity in the female offspring through T cell- and DC-associated mechanisms that are inhibited by butyrate.