Lactiplantibacillus plantarum GUANKE and Its Metabolite Phenyllactic Acid Reduce Intestinal Klebsiella pneumoniae Dysbacteriosis and Related Gut Inflammatory Injury.

Klebsiella pneumoniae (KP) is an important opportunistic pathogen that can persist in the gastrointestinal tract and serve as a reservoir for subsequent infection. The increasing prevalence of multidrug-resistant KP highlights the need for non-antibiotic strategies to limit intestinal KP burden and associated host injury. Lactiplantibacillus plantarum GUANKE (L. plantarum GUANKE) is a candidate probiotic strain with reported effects on mucosal barrier protection and inflammatory regulation, but its role in intestinal KP challenge remains unclear. In this study, the effects of L. plantarum GUANKE and its metabolite phenyllactic acid (PLA) on KP growth, intestinal KP burden, and associated inflammatory injury were investigated using antibacterial assays in vitro, metabolomic analyses, an antibiotic-pretreated mouse model of intestinal KP challenge, and an influenza A virus (IAV)/KP intestinal co-exposure model. L. plantarum GUANKE and its culture-derived products inhibited KP growth in vitro. Metabolomic analysis identified PLA as a metabolite enriched in L. plantarum GUANKE fermentation supernatants, and exogenous PLA directly inhibited KP growth in a dose-dependent manner. In an antibiotic-pretreated mouse model of intestinal KP challenge, oral administration of L. plantarum GUANKE reduced intestinal KP burden and was associated with changes in gut microbiota composition, increased cecal PLA abundance, improved intestinal barrier-related parameters, and reduced inflammatory responses, while exogenous PLA partially reproduced these effects. IAV infection increased susceptibility to intestinal KP expansion, and oral L. plantarum GUANKE reduced KP burden in the IAV/KP intestinal co-exposure model. In mice challenged with multidrug-resistant KP strain NK04152, L. plantarum GUANKE and PLA reduce intestinal KP burden and associated tissue injury in mice, supporting their potential as candidate microbiota and metabolite strategies against intestinal KP challenge.