Fecal metabolic changes in mice before Salmonella infection

ABSTRACT: With the monophasic variant of Salmonella Typhimurium (S. 4,[5],12:i-) emerging as one of the most prevalent serotypes, multidrug resistance has become an increasingly serious clinical challenge. Conventional antibiotic therapy is further constrained by adverse effects, including resistance selection, disruption of the gut microbiota, and organ toxicity. These limitations have driven growing interest in host-directed therapies (HDT) that strengthen intrinsic immune defenses and promote tissue repair to achieve sustained and balanced infection control. Here, to identify key metabolites that enhance host immunity against Salmonella infection, we compared gut metabolite profiles between non-diarrheal and diarrheal mice following S. 4,[5],12:i challenge. It revealed that diarrheal mice exhibited significantly elevated levels of 1-methylhistidine (1-MH) compared with non-diarrheal mice, indicating a marked alteration in histidine metabolism. Consistently, transcriptomic profiling together with targeted energy metabolomics indicated that histidine broadly activates immune-related programs and anti-infective responses. Mechanistically, histidine promotes M1 macrophage polarization through PI3K/AKT/mTOR/HIF-1α-dependent glycolytic reprogramming, thereby enhancing macrophage activation and controlling Salmonella infection. Collectively, our findings identify L-histidine supplementation as a promising host-directed therapeutic strategy against drug-resistant Salmonella infection.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS15911 | MetaboLights | 2026-10-04

REPOSITORIES: MetaboLights