From whole genome to probiotic candidates: a study of potentialLactobacillusstrain selection for vaginitis treatment

AbstractVaginitis is a syndrome characterized by not only the invasion of pathogens, but also the lack ofLactobacillus.Lactobacillussupplementation emerged as an innovative therapy for vaginitis which targeted the vaginal microbiota in recent years. However, limited live biotherapeutic products were explicitly marketed for this. The aim of our study is to characterize the potentialLactobacilluscandidates for enhancing the treatment of vaginitis. Initially, 98Lactobacillusisolates with whole genome were selected into the candidate pool. The genomic pathways involved in the biosynthesis of probiotic metabolites, adhering ability and acid/bile resistance, as well as sequences of antibiotic resistance genes, plasmids, transposons, viruses, and prophages were annotated. A scoring model was then established based on genomic analysis for ranking the performance of the strains, and the top-performing ones were applied toin vitrotests for sub-screening. As a result, two candidates were selected, and their probiotic abilities were verified with three reference strains.L. crispatusLG55-27 andL. gasseriTM13-16 presented outstanding ability to produce D-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity againstGardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureusandPseudomonas aeruginosathan control ones. Their acid/bile-resistant ability suggested the potential of oral supplementation. Strain LG55-27 and TM13-16 also display improved effects on pH changes, and the production of inflammation cytokines in BV model rats. This study provided a probiotic dosage recommendation for vaginitis treatment by demonstrating an effective probiotic screening pipeline based on genome sequences,in vitrotests andin vivoBV model experiment.