Detonating a "time bomb": how enteric infection stress triggers prophage induction in commensal microbiota and exacerbates disease progression.

The pathophysiology of enteric infections involves more than a straightforward pathogen-host interaction; a critical yet often underappreciated factor is the functional shift of the commensal microbiota in response to stress. This review constructs and substantiates a "Prophage-Mediated Implosion Hypothesis" to provide an integrative framework for explaining the complexities of gut infections. This hypothesis posits that during enteric infection, the stress microenvironment-generated by the pathogen, host immune responses, and clinical interventions-transforms the commensal microbiota from a "defensive barrier" into a "destructive endogenous amplifier" via prophage activation. This article systematically elucidates the three core stages of this "implosion" process: (1) how key signaling networks, represented by endogenous DNA damage (e.g., reactive oxygen species [ROS]) and exogenous agents (e.g., antibiotics), trigger the SOS response and activate prophages; (2) how prophage activation disrupts colonization resistance (via commensal lysis), mediates the horizontal transfer of virulence and resistance genes, and exacerbates inflammation (via PAMPs and the TLR9 pathway), thereby creating a destructive cascade; and (3) how this hypothesis offers novel mechanistic explanations for clinical challenges such as antibiotic-associated complications and the heterogeneity in infection severity. Finally, building on this framework, the review discusses emerging intervention strategies-such as antibiotics that spare or support bacteriophage activity and therapies targeting the SOS response to attenuate bacterial virulence. This work aims to shift the understanding of enteric infections from a traditional "external invasion" model to an integrated "combined internal and external assault" model.