Gut microbiota within-host evolution enforces colonization resistance against enteric infection

ABSTRACT:

Limited resource availability in the gut promotes competitive interactions between bacteria, which drive adaptive within-host evolution. While the role of bacterial adaptive evolution of bacterial communities has been extensively studied, its functional implications for host physiology remain unknown. Here, we show that within-host evolution of the human commensal Enterococcus faecalis confers colonization resistance to enteric Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. During gut colonization, E. faecalis evolves the ability to metabolize fructoselysine, an abundant Amadori rearrangement product generated by thermal food processing. The depletion of this diet-derived nutrient prevents S. Typhimurium colonization by restricting an essential resource. This protective mechanism was conserved across independent mouse colonies and arises via diverse evolutionary trajectories, including nucleotide polymorphisms, gene amplifications, and a horizontal gene transfer event. Additionally, analysis of E. faecalis isolates from human infants revealed that adaptation to fructoselysine availability occurs in a diet-dependent manner, with isolates from formula-fed infants utilizing fructoselysine, whereas those from breast-fed infants cannot. Conclusively, our results identify an inherent microbiome-driven self-healing mechanism, wherein bacterial evolution restores colonization resistance against enteric pathogens through nutrient depletion. Understanding these evolutionary dynamics will inform microbiome-targeted approaches to prevent and treat infectious diseases by harnessing adaptive bacterial metabolism.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic

PROVIDER: MTBLS10327 | MetaboLights | 2026-08-03

REPOSITORIES: MetaboLights