Lacticaseibacillus rhamnosus BELR47 Mitigates Inflammatory Response in a Gardnerella vaginalis-Induced Bacterial Vaginosis Mouse Model via Gut Microbiome Modulation

초록

In this study, Lacticaseibacillus rhamnosus BELR47 showed the highest lactate production, adhesion to HeLa cells, biofilm formation, and antimicrobial activity against three major bacterial vaginosis (BV)-associated pathogens: Gardnerella vaginalis, Fannyhessea vaginae, and Candida albicans. Moreover, BELR47 exerted anti-inflammatory effects in lipopolysaccharide-induced RAW 264.7 macrophages by suppressing pro-inflammatory cytokine production. In BV-induced mice, oral BELR47 administration significantly reduced vaginal exfoliation and G. vaginalis proliferation compared to the Control group. The Control group exhibited elevated serum interlukin-1 beta and increased myeloperoxidase, cyclooxygenase 2, inducible nitric oxide synthase, and tumor necrosis factor-alpha mRNA levels in the vagina, cervix, and gut, alongside decreased interlukin-10 expression, which BELR47 treatment reversed. Moreover, G. vaginalis infection diminished colonic expression of tight junction proteins (Claudin-3, Claudin-7, Occludin, ZO-1), indicating impaired gut barrier function; BELR47 ameliorated this dysfunction. BV also reduced fecal microbiome diversity, whereas BELR47 treatment restored it, as reflected by the increased levels of Butyricimonas and Lactobacillus and decreased Parasutterella. Additionally, the elevated butyric acid levels in the BELR47-treated group supported its potential to mitigate gut barrier dysfunction and alleviate intestinal inflammation. Therefore, G. vaginalis infection induces inflammation in both the vagina and colon, disrupts the gut microbiome, and alters fecal metabolites, thereby supporting the concept of a "vagina-gut axis.

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