Molecular insights into the antimicrobial and cardiometabolic functions of Lactobacillus crispatus isolated from the reproductive tract microbiota of Indian women.

BACKGROUND: Lactobacillus crispatus is a dominant member of the healthy female reproductive tract microbiota, contributing to mucosal homeostasis and pathogen exclusion. Numerous studies have highlighted the protective effects of L. crispatus against both intestinal and genital infections. In the present study, we build on this foundation to investigate the broader health-promoting properties of L. crispatus, focusing on its antimicrobial and metabolic functions; and its protective roles in hepatic and cardiometabolic disorders. METHODS: Three L. crispatus strains were selected from a panel of sixty isolates based on comprehensive genome mining analyses described in our previous publication. In the present study, we generated complete genome data for these three strains, and delineated biosynthetic pathways including their capacity for antimicrobial peptide production, lactic acid biosynthesis, short chain fatty acid synthesis and biogenic amine production. The antimicrobial activity of these isolates was assessed via agar well-diffusion assay and time-kill assay. Their ability to survive gastric pH and bile stress was evaluated through acid and bile salt tolerance assays. Further, to assess metabolic benefits, anti-steatotic and cardioprotective effects were examined in a preclinical diet-induced mouse model of cardiometabolic disorder. RESULTS: Complete genome analysis of L. crispatus strains revealed multiple antimicrobial peptide (AMP) biosynthetic gene clusters, including several novel loci associated with bacteriocins. Metabolic profiling identified pathways for bile salt metabolism, folate biosynthesis and short chain fatty acids production. Cell-free culture supernatants exhibited broad-spectrum antibacterial activity, particularly against Escherichia coli, Enterobacter hormaechei, Staphylococcus aureus and Staphylococcus haemolyticus. Further, the strains tolerated gastric pH 2 and physiological bile stress of 0.3% suggesting potential for oral administration. In vivo, oral administration of L. crispatus (108 CFU) daily for 2 weeks followed by twice-weekly for 12 weeks significantly reduced hepatic steatosis, improved insulin sensitivity and cardiac function in a diet-induced cardiometabolic disorder mouse model. This is the first report demonstrating the cardiometabolic protective potential of L. crispatus. CONCLUSIONS: L. crispatus confers diverse health benefits through pathogen resistance functions and modulation of host metabolic pathways. These findings support its potential as a novel biotherapeutic for preventing and managing hepatic and cardiometabolic disorders, extending its therapeutic relevance beyond reproductive health.