Microbiota-accessible carbohydrates enhance gut microbiota stability and antibiotic resilience through production of quorum sensing molecule AI-2

Dietary fiber and fat shape the gut microbiota and human health, yet their role in modulating the response of the microbiota to antibiotics remains underexplored. We hypothesized that dietary fiber, independent of fat content, mitigates antibiotic-induced weight loss and diarrhea in a microbiota-dependent manner. Mice were fed refined diets varying in fat and fiber contents for 6 weeks, compared to a standard plant-based chow diet. Following antibiotic administration, fiber consumption independent of fat reduced diarrhea and weight loss. High-fiber diets increased Bacteroidetes and decreased Firmicutes and Proteobacteria prior to antibiotic exposure, all of which correlated with elevated cecal short-chain fatty acids (SCFAs). Fermentable fiber increased AI-2 quorum-sensing pathway activity and improved Firmicutes resiliency to antibiotics. Supplementation with AI-2 reduced antibiotic-induced weight loss in mice fed high-fat, low-fiber diets. These findings suggest that fermentable fiber alters the gut microbiota composition and function, enhancing microbial resiliency and host tolerance to antibiotics. Dietary supplementation with microbiota-accessible fiber increased AI-2 production, stabilized Firmicutes populations, and attenuated antibiotic-associated weight loss, independent of dietary fat content.