From whole genomes to probiotic candidates: A study of potential lactobacilli strains selection for vaginitis treatment
Jinli Lyu,
Mengyu Gao,
Shaowei Zhao,
Xinyang Liu,
Xinlong Zhao,
Yuanqiang Zou,
Yiyi Zhong,
Lan Ge,
Hiafeng Zhang,
Liting Huang,
Shangrong Fan,
Liang Xiao,
Xiaowei Zhang
Affiliations
Jinli Lyu
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; BGI-Shenzhen, Shenzhen, 518083, China
Mengyu Gao
BGI-Shenzhen, Shenzhen, 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, 518083, China
Shaowei Zhao
BGI-Shenzhen, Shenzhen, 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, 518083, China
Xinyang Liu
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China
Xinlong Zhao
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
Yuanqiang Zou
BGI-Shenzhen, Shenzhen, 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, 518083, China
Yiyi Zhong
BGI Precision Nutrition (Shenzhen) Technology Co., Ltd, Shenzhen, 518083, China
Lan Ge
BGI Precision Nutrition (Shenzhen) Technology Co., Ltd, Shenzhen, 518083, China
Hiafeng Zhang
BGI Precision Nutrition (Shenzhen) Technology Co., Ltd, Shenzhen, 518083, China
Liting Huang
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China
Shangrong Fan
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Corresponding author. Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
Liang Xiao
BGI-Shenzhen, Shenzhen, 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, 518083, China; Corresponding author. BGI-Shenzhen, Shenzhen, 518083, China.
Xiaowei Zhang
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; BGI-Shenzhen, Shenzhen, 518083, China; Corresponding author. Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
Vaginitis, characterized by pathogenic invasion and a deficiency in beneficial lactobacilli, has recognized lactobacilli supplementation as a novel therapeutic strategy. However, due to individual differences in vaginal microbiota, identifying universally effective Lactobacillus strains is challenging. Traditional methodologies for probiotic selection, which heavily depend on extensive in vitro experiments, are both time-intensive and laborious. The aim of this study was to pinpoint possible vaginal probiotic candidates based on whole-genome screening. We sequenced the genomes of 98 previously isolated Lactobacillus strains, annotating their genes involved in probiotic metabolite biosynthesis, adherence, acid/bile tolerance, and antibiotic resistance. A scoring system was used to assess the strains based on their genomic profiles. The highest-scoring strains underwent further in vitro evaluation. Consequently, two strains, Lactobacillus crispatus LG55-27 and Lactobacillus gasseri TM13-16, displayed an 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 compared to reference Lactobacillus strains. Their resilience to acid and bile environments highlights the potential for oral supplementation. Oral and vaginal administration of these two strains were tested in a bacterial vaginosis (BV) rat model at various doses. Results indicated that combined vaginal administration of these strains at 1 × 106 CFU/day significantly mitigated BV in rats. This research offers a probiotic dosage guideline for vaginitis therapy, underscoring an efficient screening process for probiotics using genome sequencing, in vitro testing, and in vivo BV model experimentation.
