Subverting colonization resistance: Salmonella pathogenesis at the interface of microbiota, metabolism and inflammasome

The intestinal tract is a key immune organ and microecological system, where colonization resistance (CR) mediated by gut microbiota prevents pathogen invasion. Salmonella disrupts CR via type VI and type III secretion systems (T6SS/T3SS), inducing dysbiosis, inflammasome-driven inflammation, and intestinal barrier damage. This creates a self-reinforcing cycle:dysbiosis alters microbial metabolites, sustains inflammation, and enhances pathogen fitness, favoring chronic infection. This review integrates molecular mechanisms of microbiota disruption, inflammasome activation, and metabolic imbalance to explain how Salmonella overcomes CR. We also highlight microbiota-based countermeasures, including probiotics, natural antimicrobials, and phage therapy, as promising strategies to restore gut homeostasis.