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Lactobacillus iners at the nexus of microbiota, immunity, and pregnancy.

Pregnancy induces a dynamic reconfiguration of the vaginal microbiome, typically marked by increased dominance of Lactobacillus species and reduced microbial diversity. Among these bacteria, Lactobacillus iners stands out for its unique genomic traits, controversial associations with vaginal health, and frequent presence across all stages of gestation. This review synthesizes current literature on the maternal microbiome with a focus on L. iners, exploring its strain-level diversity, metabolic idiosyncrasies, and inflammatory potential. We discuss how host factors such as ethnicity, sexual activity, maternal age, and especially obesity, influence microbial composition, and evaluate conflicting data surrounding L. iners in contexts like in vitro fertilization, preterm birth, and postpartum recovery. Emerging evidence suggests that L. iners may act as a transitional species, whose effect on pregnancy outcomes depends on its abundance, genetic features, and interactions with the host immune system. We also assess limitations of current animal models and propose future directions for understanding this enigmatic bacterium. Unraveling the role of L. iners will be essential to predicting, preventing, and managing adverse pregnancy outcomes in diverse populations.

Humans

Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

Vaginosis, Bacterial

Human Milk Oligosaccharides Modulate Nitrogen Utilization in Lactobacillus crispatus in a Glucose-Dependent Manner.

The vaginal microbiome's transition to a dysbiotic state increases susceptibility to pathogens like group B Streptococcus. While human milk oligosaccharides are established prebiotics in the neonatal gut, their impact on the vaginal niche remains largely unexplored. This study investigated the effects of pooled human milk oligosaccharides on the growth and physiology of vaginal (Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners) and gut-derived (Lactobacillus reuteri, Lactobacillus rhamnosus) commensals. Growth analyses revealed that human milk oligosaccharides significantly and selectively stimulated growth across all vaginal strains tested, whereas gut commensals exhibited variable or inhibited growth. Carbohydrate utilization assays and comparative genomics against Bifidobacterium infantis showed that Lactobacillus crispatus and Lactobacillus reuteri lack the canonical metabolic machinery to catabolize human milk oligosaccharides. Instead, nitrogen utilization assays identified a glucose-dependent pathway where human milk oligosaccharides are associated with the depletion of primary amines and amino acids in Lactobacillus crispatus supernatants. These results suggest that human milk oligosaccharides act as noncatabolic modulators of vaginal lactobacilli. Collectively, these in vitro findings may warrant investigation of human milk oligosaccharides as modulators of vaginal commensal physiology in more complex experimental systems.

Humans

From dysbiosis to homeostasis: Oleic acid matters in the vagina.

The role of fatty acids in shaping vaginal microbiota remains unclear. In an issue of Cell, Zhu et al. use genomic and transcriptomic analyses to reveal that oleic acid (OA) selectively inhibits L. iners while promoting L. crispatus, suggesting new strategies for the treatment of bacterial vaginosis (BV).

Female