C19orf18 modulates host susceptibility to Salmonella Typhimurium infection via remodeling of the gut microbiota and tryptophan metabolism

Chromosome 19 open reading frame 18 (C19orf18) is a protein-coding gene. On the basis of our preliminary findings, C19orf18 is selectively upregulated in the intestine of mice during Salmonella Typhimurium ( S . Tm) infection; however, its biological significance and functional role in the course of infection remain unclear. Here, we identify C19orf18 as a host factor associated with S . Tm-induced intestinal inflammation. Consistent results from both in vivo and in vitro experiments demonstrated that loss of C19orf18 function markedly attenuated S . Tm-induced intestinal inflammation and promoted mucosal injury repair. Mechanistically, C19orf18 deficiency was associated with the infection-associated gut ecosystem characterized by enrichment and expansion of Verrucomicrobiota, particularly the beneficial genus Akkermansia , and was associated with amino acid metabolic remodeling characterized by altered tryptophan-associated metabolic profiles. These tryptophan-associated metabolites were associated with epithelial restitution and suppression of inflammatory responses. Collectively, our findings reveal a previously unrecognized mechanism by which C19orf18 modulates host responses to a foodborne enteric pathogen and support a functional relationship among C19orf18-associated microbiota alterations, metabolic changes, and intestinal inflammatory outcomes.