Mechanism of Legionella pneumophila-induced liver injury via gut microbiota translocation under immunosuppression.

Abstract

Legionnaires' disease presents substantial clinical challenges in immunocompromised patients, with the pathogenesis of multi-organ dysfunction remaining poorly understood. Through an immunosuppressed guinea pig model, we demonstrate that Legionella pneumophila (Lp) infection triggers a systemic pathological cascade that extends beyond pulmonary damage. Our results show that Lp infection not only induces severe pulmonary inflammation and endothelial barrier disruption but also initiates gut-liver axis injury mediated by intestinal microbiota dysbiosis. Metagenomic sequencing revealed specific enrichment of Anoxybacillus kestanbolensis and Geobacillus vulcani in both intestinal and hepatic tissues post-infection, indicating microbial translocation. This bacterial dissemination was associated with enhanced hepatocyte apoptosis and exacerbated liver injury. Mechanistically, we demonstrate that Lp infection compromises intestinal epithelial integrity, promotes translocation of enteric pathogens, and subsequently activates hepatic apoptotic pathways, thereby aggravating systemic inflammation and multi-organ failure. These findings elucidate the gut microbiota-gut-liver axis as a pivotal mechanism in Lp-induced systemic damage and suggest potential therapeutic targets for severe Legionnaires' disease in immunocompromised hosts.