Microbiota-derived metabolites act as ecological effectors of colonization resistance against Salmonella Enteritidis

ABSTRACT:

Colonization resistance is a fundamental ecological function of the gut microbiota that limits the expansion of enteric pathogens. Yet, the microbial effectors linking ecosystem homeostasis to pathogen control remain poorly understood. Here, we demonstrate that Salmonella Enteritidis (S. Enteritidis) reshapes the intestinal ecosystem by reprogramming microbial functions and metabolic profiles. Fecal microbiota transplantation (FMT) markedly alleviated disease, restored the functional capacity of the microbiome, and attenuated host inflammatory responses despite incomplete reconstruction of donor microbial composition. Microbiota-derived metabolites emerged as key functional mediators of these protective effects. These metabolites inhibited Salmonella biofilm formation and epithelial invasion by remodeling bacterial metabolic programs. Furthermore, metabolites produced by two commensal isolates, GK-6 and GK-11, recapitulated the protective effects of the complete fecal metabolite pool and exhibited conserved metabolic signatures associated with biofilm suppression. These findings establish microbiota-derived metabolites as ecological effectors of colonization resistance and provide a framework for developing defined metabolite-based therapeutics as an alternative to FMT. arrow_drop_uphide

INSTRUMENT(S): Gas Chromatography MS - positive - low-polarity, Gas Chromatography MS - negative - low-polarity

PROVIDER: MTBLS15505 | MetaboLights | 2026-08-31

REPOSITORIES: MetaboLights