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

Abstract

Vaginitis is a syndrome characterized by not only the invasion of pathogens, but also the lack of Lactobacillus. Lactobacillus supplementation 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 potential Lactobacillus candidates for enhancing the treatment of vaginitis. Initially, 98 Lactobacillus isolates 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 to in vitro tests for sub-screening. As a result, two candidates were selected, and their probiotic abilities were verified with three reference strains. L. crispatus LG55-27 and L. gasseri TM13-16 presented outstanding ability to produce D-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity against Gardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa than 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 vitro tests and in vivo BV model experiment.

Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis

“…Similarly, Husain et al showed that the colonization rate of the intervention strains and the diversity of the vaginal microbiome did not differ between the probiotic and control groups (49). In fact, L. gasseri TM13 and L. crispatus LG55 used in this study were isolated, cultured, and screened from the human intestine (33). Existing research has shown that there are still many differences in environmental adaptability and systematic developmental characteristics between Lactobacillus strains isolated from the intestine and those isolated from the vagina.…”

“…The probiotic strains used in this study are L. gasseri TM13 and L. crispatus LG55 which were isolated from the feces of 2 healthy Chinese people, which we developed in-house. They showed the strong ability to lower vaginal pH, inhibit the growth of pathogenic bacteria and fungi, and alleviated the inflammatory response of BV rats (33). In this study, we aim at evaluating the effectiveness of oral Chinese-origin probiotic strains, L. gasseri TM13 and L. crispatus LG55, with adjuvant MET in treating Chinese BV patients, and investigate the dynamic of the intestine and vaginal microbiome using metagenomic sequencing during the trial.…”

Orally administratedLactobacillus gasseriTM13 andLactobacillus crispatusLG55 Can Restore the Vaginal Health of Patients Recovering from Bacterial Vaginosis

“…Similarly, Husain et al showed that the colonization rate of the intervention strains and the diversity of the vaginal microbiome did not differ between the probiotic and control groups (Husain et al, 2020). In fact, L. gasseri TM13 and L. crispatus LG55 used in this study were isolated, cultured, and screened from the human intestine (Lyu et al, 2022). Further evaluation on whether the differences in the physicochemical environment and differences in patterns of interactions between bacteria in the vagina and the intestine (Human Microbiome Project, 2012) can prevent the transfer of the intervening strains from the intestine to the vagina is needed.…”

“…A random number table generated by SPSS 13.0 software was used to randomly assign subjects to the control or probiotic group using a 1:1 ratio. After enrollment, the probiotic group received MET vaginal suppositories (200 mg daily for 7 days) along with oral intake of probiotic solid drinks containing L. gasseri TM13 and L. crispatus LG55 (Lyu et al, 2022) (daily intake ≥ 5×10 9 CFU for 30 days); the control group received the same dose of MET vaginal suppositories.…”

“…The probiotic strains used in this study are L. gasseri TM13 and L. crispatus LG55 which were isolated from the feces of 2 healthy Chinese people, which we developed in-house. They showed the strong ability to lower vaginal pH, inhibit the growth of pathogenic bacteria and fungi, and alleviated the inflammatory response of BV rats (Lyu et al, 2022). In this study, we aim at evaluating the effectiveness of oral Chinese-origin probiotic strains, L. gasseri TM13 and L. crispatus LG55, with adjuvant MET in treating Chinese BV patients, and investigate the dynamic of the gut and vaginal microbiome using metagenomic sequencing during the trial.…”