Lipoteichoic Acid from Enterococcus faecalis Triggers Murine Pneumonia via Gut-Lung Axis Dysregulation and Immune Cell Recruitment.

Pediatric pneumonia poses a substantial respiratory risk to infants and toddlers under three years of age, exacerbated by the widespread clinical misuse of antibiotics. Since diarrhea is frequently observed in pediatric patients with pneumonia, we sought to explore the potential gut-lung interaction. To this end, we isolated and identified a pathogenic Enterococcus faecalis (LE) strain from the intestinal tract of affected children, which could induce pneumonia-like symptoms in juvenile mice. LE-LTA, a proinflammatory component derived from Enterococcus faecalis, was associated with pneumonia-like inflammatory pathology in juvenile mice and concurrent disturbances in the gut-lung system. LE-LTA exposure was accompanied by increased levels of proinflammatory cytokines and accumulation of macrophage-like cells in intestinal and lung tissues, consistent with enhanced local inflammatory responses and tissue injury. In addition, LE-LTA was associated with reduced pulmonary tight-junction protein expression (Occludin and Claudin-1), suggesting impaired barrier integrity. Moreover, LE-LTA treatment was accompanied by altered microbial community profiles in both the gut and lung samples. Together, these findings suggest that LE-LTA may contribute to pneumonia-like pathology with gut-lung dysregulation in juvenile mice. These findings uncover a previously unrecognized gut-lung interaction mechanism in pediatric pneumonia, highlighting promising therapeutic targets for clinical translation.