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<p>Vaginal disorders are prevalent health concerns primarily driven by vaginal dysbiosis, yet antibiotic treatment often leads to recurrence and disruption of the vaginal microbiota. Probiotic therapy is promising, but current development focuses mainly on host-adapted species, which are reported to be sensitive to dynamic vaginal pH and nutrient. To broaden the candidate repertoire, we investigated whether <i>Limosilactobacillus fermentum</i>, a “nomadic” species that transitions between hosts and environments, could serve as a vaginal probiotic. We conducted a population-scale genomic evaluation of the vaginal probiotic potential of <i>L. fermentum</i> (211 public genomes and 2 vaginal isolates) and confirmed its nomadic genomic features: an open pangenome, larger genome size and GC content, and a lack of geographic- or source-specific clustering in the phylogenetic tree. Functional annotation identified 35 core genes associated with vaginal probiotic traits, 9 KEGG pathways enriched in metabolism and 51 CAZyme subfamilies. Virulence and antibiotic resistance genes were rare. A representative strain, VL9, isolated from a healthy vagina, was validated in vitro, exhibiting robust growth across pH 3–7, stable lactic acid production (13.0&#xa0;g/L in nutrient-rich medium and 5.4&#xa0;g/L in oligotrophic medium), high cell surface hydrophobicity (&gt; 95%), and broad inhibition against 14 of 15 pathogens, with &gt; 98% growth inhibition at 10<sup>4</sup>–10<sup>6</sup>&#xa0;CFU/mL against <i>Candida albicans</i>. VL9 also exhibited low MICs to 11 antibiotics (≤ 4&#xa0;µg/mL) and non-hemolytic activity. Our findings provide insight into broadening candidate species for vaginal probiotics and position VL9 as a potential strain for further validation.</p>

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Vaginal Probiotic Potential of the Nomadic Species Limosilactobacacillus fermentum Under Dysbiotic Vaginal Conditions: Population Genomic Insights and Anti-Pathogenic Efficacy of a Vaginal Isolate VL9

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Yanqing Che,
  • Yixin Mao,
  • Mengjie Li,
  • Xiao Liu,
  • Hongzhou Li,
  • Guodong Yan,
  • He Gao,
  • Xuemei Bai,
  • Zhiwen Sun,
  • Xiaoning Liu,
  • Duochun Wang

摘要

Vaginal disorders are prevalent health concerns primarily driven by vaginal dysbiosis, yet antibiotic treatment often leads to recurrence and disruption of the vaginal microbiota. Probiotic therapy is promising, but current development focuses mainly on host-adapted species, which are reported to be sensitive to dynamic vaginal pH and nutrient. To broaden the candidate repertoire, we investigated whether Limosilactobacillus fermentum, a “nomadic” species that transitions between hosts and environments, could serve as a vaginal probiotic. We conducted a population-scale genomic evaluation of the vaginal probiotic potential of L. fermentum (211 public genomes and 2 vaginal isolates) and confirmed its nomadic genomic features: an open pangenome, larger genome size and GC content, and a lack of geographic- or source-specific clustering in the phylogenetic tree. Functional annotation identified 35 core genes associated with vaginal probiotic traits, 9 KEGG pathways enriched in metabolism and 51 CAZyme subfamilies. Virulence and antibiotic resistance genes were rare. A representative strain, VL9, isolated from a healthy vagina, was validated in vitro, exhibiting robust growth across pH 3–7, stable lactic acid production (13.0 g/L in nutrient-rich medium and 5.4 g/L in oligotrophic medium), high cell surface hydrophobicity (> 95%), and broad inhibition against 14 of 15 pathogens, with > 98% growth inhibition at 104–106 CFU/mL against Candida albicans. VL9 also exhibited low MICs to 11 antibiotics (≤ 4 µg/mL) and non-hemolytic activity. Our findings provide insight into broadening candidate species for vaginal probiotics and position VL9 as a potential strain for further validation.