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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bacterial vaginosis (BV) is a prevalent vaginal dysbiosis primarily associated with\n                      <jats:italic>Gardnerella vaginalis<\/jats:italic>\n                      (\n                      <jats:italic>G. vaginalis<\/jats:italic>\n                      ). However, its pathogenic mechanisms remain incompletely understood, particularly the interplay between microbial dysbiosis and host metabolic perturbations. In this study, a\n                      <jats:italic>G. vaginalis<\/jats:italic>\n                      -associated BV-like rat model was established, and integrated multi-omics analysis was performed to characterize its inflammatory landscape.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Female Sprague-Dawley rats received antibiotic pretreatment followed by intravaginal inoculation with\n                      <jats:italic>G. vaginalis<\/jats:italic>\n                      to establish a BV-like model. Gram staining, histological examination, and serum cytokine enzyme-linked immunosorbent assay (ELISA) evaluated the model phenotype. 16S rRNA gene sequencing characterized the vaginal microbiota, and UHPLC\u2013MS\/MS profiled the vaginal metabolome. ELISA quantified serum metabolites. Western blotting (WB) assessed proteins related to Toll-like receptor (TLR)\/nuclear factor-kappa B (NF-\u03baB) signaling in uterine tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The BV-like phenotype was characterized by clue cell-like epithelial cells, histopathological injury, and an altered serum cytokine profile. 16S sequencing revealed nonsignificant trends toward increased diversity and reduced evenness in the model group. Although overall microbial community composition did not differ significantly between groups, within-group dispersion was significantly lower in the model group. The genera\n                      <jats:italic>Gardnerella<\/jats:italic>\n                      ,\n                      <jats:italic>Staphylococcus<\/jats:italic>\n                      ,\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      , and\n                      <jats:italic>Aerococcus<\/jats:italic>\n                      were overrepresented, whereas\n                      <jats:italic>Collinsella<\/jats:italic>\n                      was underrepresented; among these genera only\n                      <jats:italic>Aerococcus<\/jats:italic>\n                      remained significant after FDR correction. Untargeted vaginal metabolomics and targeted serum measurements indicated enhanced arachidonic acid (AA)-related metabolism and compartment-specific remodeling of tryptophan (TRP) metabolism. Group-adjusted partial correlation analysis identified nominal positive correlations of\n                      <jats:italic>Gardnerella<\/jats:italic>\n                      with AA and\n                      <jats:italic>Collinsella<\/jats:italic>\n                      with 5-hydroxyindole-3-acetic acid (5-HIAA), as well as a nominal negative correlation of\n                      <jats:italic>Blastococcus<\/jats:italic>\n                      with thromboxane B\n                      <jats:sub>2<\/jats:sub>\n                      (TXB\n                      <jats:sub>2<\/jats:sub>\n                      ); however, none remained significant after FDR correction. WB revealed increased abundance of uterine proteins associated with TLR2\/4\u2013NF-\u03baB\u2013COX-2 inflammatory signaling in the model group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings suggest that the\n                      <jats:italic>G. vaginalis<\/jats:italic>\n                      -associated BV-like phenotype is linked to vaginal microbial alterations, enhanced AA-related metabolism, compartment-specific remodeling of TRP metabolism, and upregulation of proteins related to uterine TLR\/NF-\u03baB inflammatory signaling. This microbiome\u2013metabolome\u2013immune network may help explain how\n                      <jats:italic>G. vaginalis<\/jats:italic>\n                      -associated vaginal dysbiosis contributes to BV-like inflammatory changes and may be related to endometrial inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1914434","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:38:53Z","timestamp":1790055533000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory landscape of Gardnerella vaginalis-associated bacterial vaginosis in rats: an integrated multi-omics analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiao-Feng","family":"Ruan","sequence":"first","affiliation":[{"name":"Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]},{"name":"The Second Affiliated Hospital of Guangzhou 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