Metabolic strategies of Enterobacteriaceae gut colonization

Enterobacteriaceae are facultative anaerobic bacteria that commonly colonize the gut and include both commensals and diverse pathogens. They can flexibly adapt their metabolic strategy to grow in the intestinal environment. As Enterobacteriaceae blooms are linked to enteric disease and the dissemination of antibiotic resistance, a deeper understanding of the factors that drive their expansion is needed. In the healthy intestine, Enterobacteriaceae subsist on low concentrations of diet-derived and mucus-derived monosaccharides that feed glycolysis and mixed-acid fermentation. Inflammation reshapes this niche as immune-derived oxidants generate new terminal electron acceptors, such as nitrate or tetrathionate, and facilitate oxygen diffusion into the gut lumen, thereby expanding facultative anaerobes and broadening the range of usable substrates. In this Review, we discuss recent evidence across Escherichia coli, Citrobacter rodentium, Klebsiella spp. and Salmonella Typhimurium to define a conserved, monosaccharide-fuelled programme for colonization and its inflammatory remodelling. Competition with commensal bacteria for these nutrients underpins colonization resistance, and genetic differences can determine competitive fitness. Metabolism lies at the core of these ecological dynamics, and recognizing its central role will help guide the design of future therapies.