Abstract

Lactobacillus crispatus is the dominant species in the vagina of many women. With the potential for strains of this species to be used as a probiotic to help prevent and treat dysbiosis, we investigated isolates from vaginal swabs with Lactobacillus-dominated and a dysbiotic microbiota. A comparative genome analysis led to the identification of metabolic pathways for synthesis and degradation of three major biogenic amines in most strains. However, targeted metabolomic analysis of the production and degradation of biogenic amines showed that certain strains have either the ability to produce or to degrade these compounds. Notably, six strains produced cadaverine, one produced putrescine, and two produced tyramine. These biogenic amines are known to raise vaginal pH, cause malodour, and make the environment more favourable to vaginal pathogens. In vitro experiments confirmed that strains isolated from women with a dysbiotic vaginal microbiota have higher antimicrobial effects against the common urogenital pathogens Escherichia coli and Enterococcus faecium. The results indicate that not all L. crispatus vaginal strains appear suitable for probiotic application and the basis for selection should not be only the overall composition of the vaginal microbiota of the host from which they came, but specific biochemical and genetic traits.

Highlights

  • As the dominant organism in the vagina of many healthy women, Lactobacillus crispatus is thought to be an important contributor to reproductive health [1]

  • The species has been postulated to be an excellent candidate for probiotic use to restore and maintain vaginal health [2]

  • Given the high incidence of conditions that result from vaginal dysbiosis [3,4,5], including urinary tract infection (UTI) and bacterial vaginosis (BV), as well as an increased risk of sexually transmitted diseases and preterm labour [5], the vaginal administration of one strain of Lactobacillus crispatus has been pilot tested to improve women’s health [6]

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Summary

Introduction

As the dominant organism in the vagina of many healthy women, Lactobacillus crispatus is thought to be an important contributor to reproductive health [1]. Data obtained in vitro showed that other two strains (i.e., RL16 and RL14) can produce tyramine when grown in conditions that simulate the vaginal environment ( strain RL20 was not available for this analysis) These findings have implications for products using L. crispatus ostensibly for vaginal health, as potentially some of these strains may produce malodorous compounds. Antimicrobial activity was significantly higher in the strains isolated from dysbiotic patients, suggesting adaptation due to be sourced from more competitive environments This inhibitory activity ceased following treatment with the protease trypsin, and heating of the supernatants to 85 ◦C for 45 min, indicating that the observed antimicrobial properties resulted from a heat-labile protein. The option of using probiotic L. crispatus strains to this end, is worthy of further study, but specific, well-documented characteristics must guide the selection

Bacterial Strains Used in This Study
Phylogenetic and Functional Genomics Analyses
LC-MS Protocol
Metabolite Identification
Biogenic Amines Pathway Analysis
Agar Well Diffusion Assays
Findings
Statistical Analysis
Full Text
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