An anaerobic pathogen operates oxidative metabolism to colonize the inflamed intestine

To colonize the densely populated large intestine and cause disease, enteric pathogens must deploy their virulence factors to establish distinct nutrient niches. While facultative anaerobes exploit inflammation-induced oxygenation to gain a competitive advantage, how obligate anaerobic pathogens construct nutrient niches for colonization remains poorly understood. Here we show that enterotoxigenic Bacteroides fragilis (ETBF) an obligate anaerobe implicated in colitis and colorectal cancer, uses its virulence factor, Bacteroides fragilis toxin (BFT), to reprogram intestinal epithelial cell metabolism. BFT activates pro-tumorigenic signaling and hijacks the host bile acid recycling pathway, inducing a metabolic shift in the epithelium from oxidative phosphorylation to glycolysis. This shift increases intestinal lactate and oxygen, nutrients that fuel ETBF's own oxidative metabolism. These findings reveal an unexpected strategy by which an obligate anaerobe generates and exploits an oxidative niche in the inflamed gut, redefining how microbial virulence factors shape host metabolism to promote pathogen persistence.