An Anaerobic Pathogen Rewires Host Metabolism to Fuel Oxidative Growth in the Inflamed Gut

To colonize their host and cause disease, enteric pathogens must deploy their virulence factors to establish distinct nutrient niches. How anaerobic pathogens construct nutrient niches in the densely populated large intestine remains poorly understood. Enterotoxigenic Bacteroides fragilis (ETBF) is a classically anaerobic bacterium implicated in inflammation-associated diseases, including colitis and colorectal cancer. Here, we show that ETBF uses its virulence factor, Bacteroides fragilis toxin (BFT), to generate and adapt to a localized oxidative niche that supports gut colonization. BFT manipulates colonic epithelial signaling and the bile acid recycling pathway, inducing a metabolic shift in the epithelium from oxidative phosphorylation to glycolysis. This shift increases local concentrations of lactate and oxygen, nutrients that support oxidative metabolism in ETBF. These findings reveal an unexpected strategy by which a classically anaerobic pathogen leverages host metabolic remodeling to generate and exploit an oxidative niche in the inflamed gut.