Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation.

Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners-dominated microbial communities are associated with poorer outcomes, including higher risk of bacterial vaginosis (BV), compared with vaginal microbiota rich in L. crispatus. Unfortunately, standard-of-care metronidazole therapy for BV typically results in dominance of L. iners, probably contributing to post-treatment relapse. Here we generate an L. iners isolate collection comprising 34 previously unreported isolates from 14 South African women with and without BV and 4 previously unreported isolates from 3 US women. We also report an associated genome catalogue comprising 1,218 vaginal Lactobacillus isolate genomes and metagenome-assembled genomes from >300 women across 4 continents. We show that, unlike L. crispatus, L. iners growth is dependent on L-cysteine in vitro and we trace this phenotype to the absence of canonical cysteine biosynthesis pathways and a restricted repertoire of cysteine-related transport mechanisms. We further show that cysteine concentrations in cervicovaginal lavage samples correlate with Lactobacillus abundance in vivo and that cystine uptake inhibitors selectively inhibit L. iners growth in vitro. Combining an inhibitor with metronidazole promotes L. crispatus dominance of defined BV-like communities in vitro by suppressing L. iners growth. Our findings enable a better understanding of L. iners biology and suggest candidate treatments to modulate the vaginal microbiota to improve reproductive health for women globally.

Optimizing availability of obstetric surgical care in India: A cost-effectiveness analysis examining rates and access to Cesarean sections.

The objective of this study is to assess the cost-effectiveness of three different strategies with different availabilities of cesarean sections (CS). The setting was rural and urban areas of India with varying rates of CS and access to comprehensive emergency obstetric care (CEmOC) for women of reproductive age in India. Three strategies with different access to CEmOC and CS rates were evaluated: (A) India's national average (50.2% access, 17.2% CS rate), (B) rural areas (47.2% access, 12.8% CS rate) and(C) urban areas (55.7% access, 28.2% CS rate). We performed a first-order Monte Carlo simulation using a 1-year cycle time and 34-year time horizon. All inputs were derived from literature. A societal perspective was utilized with a willingness-to-pay threshold of $1,940. The outcome measures were costs and quality-adjusted life years were used to calculate the incremental cost-effectiveness ratio (ICER). Maternal and neonatal outcomes were calculated. Strategy C with the highest access to CEmOC despite the highest CS rate was cost-effective, with an ICER of 354.90. Two-way sensitivity analysis demonstrated this was driven by increased access to CEmOC. The highest CS rate strategy had the highest number of previa, accreta and ICU admissions. The strategy with the lowest access to CEmOC had the highest number of fistulae, uterine rupture, and stillbirths. In conclusion, morbidity and mortality result from lack of access to CEmOC and overuse of CS. While interventions are needed to address both, increasing access to surgical obstetric care drives cost-effectiveness and is paramount to optimize outcomes.

Effect of commercial vaginal products on the growth of uropathogenic and commensal vaginal bacteria.

Half of postmenopausal women experience genitourinary syndrome of menopause, for which many use lubricating vaginal products. The effect of vaginal products on uropathogenic and commensal vaginal bacteria is poorly understood. We evaluated the effect of five common vaginal products (KY Jelly, Replens Silky Smooth lubricant, coconut oil, Replens Long-Lasting moisturizer or Trimo-San) on growth and viability of Escherichia coli and Lactobacillus crispatus. Bacteria were co-cultured products alone and in the presence of both vaginal epithelial cells and selected products. Bacterial growth was compared between conditions using an unpaired t-test or ANOVA, as appropriate. All products except for coconut oil significantly inhibited growth of laboratory and clinical strains of Escherichia coli (p < 0.02). Only two products (Replens Long-Lasting moisturizer and Trimo-San) significantly inhibited growth of Lactobacillus crispatus (p < 0.01), while the product Replens Silky Smooth stimulated growth (p < 0.01). Co-culture of selected products in the presence of vaginal epithelial cells eliminated the inhibitory effects of the products on E. coli. In conclusion, in vitro exposure to vaginal moisturizing and lubricating products inhibited growth of Escherichia coli, though the inhibition was mitigated by the presence of vaginal epithelial cells. Lactobacillus crispatus demonstrated less growth inhibition than Escherichia coli.