Specific microbial communities in the female genital tract are linked to health outcomes; for example, a microbiome deficient in Lactobacillus is observed in bacterial vaginosis. However, available therapies may not effectively promote the growth of beneficial bacterial species that could prevent the recurrence of disease. Writing in Cell, Zhu et al. propose that targeting unsaturated long-chain fatty acids (uLCFAs) might differentially modulate vaginal lactobacilli, offering a novel strategy for treating bacterial vaginosis.

uLCFAs serve as building blocks for bacterial membranes, but also possess antimicrobial activity against certain bacterial species. The authors assessed the impact of cis-9-uLCFAs, such as oleic acid, on the growth of various Lactobacillus species. They found that oleic acid selectively inhibited L. iners while promoting the growth of other species, including the health-associated L. crispatus. Transcriptomic analysis revealed that oleic acid treatment upregulates a putative fatty acid efflux pump (farE) and oleate hydratase (ohyA) in other species but not in L. iners. farE was shown to be essential for oleic acid resistance, whereas ohyA converts oleic acid for use in phospholipid synthesis. Oleic acid treatment, either alone or combined with the antibiotic metronidazole, shifted the dominance of bacterial vaginosis-like communities towards L. crispatus in vitro.