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Exopolysaccharides of Lactobacillus crispatus mediate key balancing interactions with the vaginal mucosa.

  • 2026-02-19
  • NPJ biofilms and microbiomes 12(1)
    • Vanessa Croatti
    • Caroline Dricot
    • Tom Eilers
    • Jelle Dillen
    • Tim Van Rillaer
    • Eline Cauwenberghs
    • Ilke Van Tente
    • Sam Bakelants
    • Dieter Vandenheuvel
    • Camille Allonsius
    • Isabel Pintelon
    • Sofie Thys
    • Wendy Mensah
    • Marina Naldi
    • Peter A Bron
    • Stijn Wittouck
    • Irina Spacova
    • Carola Parolin
    • Beatrice Vitali
    • Sarah Lebeer

Study Design

Population
human vaginal samples of healthy volunteers
Methods
integrate bacterial genetics, in vitro epithelial systems, human-derived data and proteomic approach (Olink®); Functional disruption of epsE; In human vaginal epithelial monolayers and a 3D vaginal organotypic model
Lactobacillus crispatus is a dominant member of the healthy vaginal microbiota, yet the mechanisms by which it modulates host immunity remain poorly defined, in part due to the lack of tractable in vivo models. Here, we integrate bacterial genetics, in vitro epithelial systems, human-derived data and proteomic approach (Olink®) to uncover a critical role for L. crispatus exopolysaccharides (EPS) in shaping the bacteria-vagina interactions. Comparative genomics identified a conserved EPS biosynthetic locus, with the priming glycosyltransferase gene epsE emerging as a regulatory node, in line with its distinct expression in human vaginal samples. Functional disruption of epsE abrogated L. crispatus EPS production and revealed its role for immune modulation. In human vaginal epithelial monolayers, EPS presence enhanced immune-regulatory (LAP TGF-beta-1) and anti-inflammatory (CST5) responses, whereas its absence triggered elevated pro-inflammatory cytokines (IL1β, IL6, IL8) and matrix metalloproteinase (MMP10). In a 3D vaginal organotypic model, EPS increased chemokines (CXCL5, CXCL6) linked to immune surveillance and the presence of the markers was validated in vaginal samples of healthy volunteers. These findings position EPS as a key immunomodulatory structure of L. crispatus, advancing our mechanistic understanding of host-commensal interactions and informing microbiome-based strategies to promote vaginal health.

Research Insights

  • Lactobacillus crispatus→Improved Immune Regulation

    EPS presence enhanced immune-regulatory (LAP TGF-beta-1) and anti-inflammatory (CST5) responses, whereas its absence triggered elevated pro-inflammatory cytokines (IL1β, IL6, IL8) and matrix metalloproteinase (MMP10).

    Effect
    Beneficial
    Effect size
    Moderate
  • Lactobacillus crispatus→Improved Immune Surveillance

    In a 3D vaginal organotypic model, EPS increased chemokines (CXCL5, CXCL6) linked to immune surveillance and the presence of the markers was validated in vaginal samples of healthy volunteers.

    Effect
    Beneficial
    Effect size
    Moderate
  • Lactobacillus crispatus→Reduced Vaginal Inflammation

    EPS presence enhanced immune-regulatory (LAP TGF-beta-1) and anti-inflammatory (CST5) responses, whereas its absence triggered elevated pro-inflammatory cytokines (IL1β, IL6, IL8) and matrix metalloproteinase (MMP10).

    Effect
    Beneficial
    Effect size
    Moderate
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