Repurposing Host Defense and Microbial Metabolism for Salmonella Gut Colonization

ABSTRACT

Salmonella enterica serovar Typhimurium ( S Tm) is a leading cause of diarrheal disease and efficiently colonizes the gut lumen despite microbiota‐mediated colonization resistance. Emerging evidence indicates that S Tm does not simply evade or overcome these barriers, but instead exploits host immune responses and microbiota‐derived metabolic activities to create a permissive intestinal niche. In this review, we discuss recent advances in our understanding of S Tm gut colonization, with a focus on how host antimicrobial factors and microbiota‐derived metabolites are repurposed to promote pathogen growth, motility, and invasion. We highlight findings showing that the antimicrobial lectin RegIIIβ, together with microbiota‐dependent metabolites such as fatty acid‐derived cues and polyamines, can unexpectedly facilitate S Tm colonization. Together, these studies support a model in which host defense programs and microbial metabolism are redirected to promote pathogen fitness, revealing potential therapeutic opportunities for controlling enteric infections.