Acarbose redirects gut microbiome utilization of dietary carbohydrates to suppress anaphylaxis in mice

Abstract Microbiota-accessible carbohydrates modulate host immunity by shaping gut microbial composition and metabolism. However, their role in modulating the microbiota to influence allergic responses is unclear. Here we show that a widely used antidiabetic agent, the α-glucosidase inhibitor acarbose, redirects dietary carbohydrate utilization by gut bacteria to suppress mast-cell-dependent anaphylaxis in mice, independently of adaptive immune responses. Enhanced carbohydrate availability promoted the proliferation of Parabacteroides distasonis in the mouse gut, leading to increased succinate abundance and intracellular NAD + levels, and reduced reliance on b-type cytochrome-dependent anaerobic respiration. Direct administration of succinate suppressed systemic anaphylaxis and mast cell degranulation in vitro, implicating succinate as a key effector. A human cohort analysis revealed that patients treated with α-glucosidase inhibitors showed a lower incidence of anaphylaxis than untreated individuals. These findings uncover a previously unrecognized gut-microbiota-mediated pathway linking dietary carbohydrate metabolism to systemic immune regulation.