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A total of 164 women were included in this study analysis with a ratio of 1:3 for HPV positive and HPV negative women. The V3\u2010V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) followed by sequencing with Illumina. Untargeted metabolomic sequencing was conducted by the liquid chromatography\u2010mass spectrometry (LC\u2010MS) system. Specific microbial species and differentially expressed metabolites associated with these differences were explored. We found that a statistically significant difference existed in the bacterial structure between HPV positive and HPV negative women (<jats:italic>R<\/jats:italic>\u2009=\u20090.2177, <jats:italic>p<\/jats:italic>\u2009=\u20090.001), and HPV positivity was associated with the enrichment of <jats:italic>Lactobacillus iners<\/jats:italic> among women diagnosed with vaginitis. However, this difference was not observed in women without vaginitis. Regarding metabolic differences, HPV positive women with vaginitis displayed elevated levels of organic acids and their derivatives, accompanied by decreased lipid levels in their vaginal secretions. Conversely, HPV positive women without vaginitis showed higher lipid levels and lower concentrations of organic acids and their derivatives. Among women with vaginitis, <jats:italic>Lactobacillus iners<\/jats:italic> was positively correlated with biogenic amine, organic acids and derivatives and negatively correlated with kessyl glycol. Among women without vaginitis, <jats:italic>Lactobacillus iners<\/jats:italic> was negatively correlated with pelargonic acid. The disparity in the abundance and metabolites of vaginal microbiota between HPV positive and HPV negative women could be affected by whether the woman has been diagnosed with vaginitis. Metabolic differences indicated that antioxidant therapy holds promising prospects for potential application in the management and treatment of HPV infections. Further in\u2010depth research into the molecular mechanisms is crucial for clarifying the precise role that vaginal microbiota and metabolites play in HPV infection.<\/jats:p>","DOI":"10.1002\/jmv.70385","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T10:52:42Z","timestamp":1746528762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vaginal Microbiome and Metabolome Profiles Among HPV Positive and HPV Negative Women Based on Stratification of Vaginitis"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-5327","authenticated-orcid":false,"given":"Shuang","family":"Zhao","sequence":"first","affiliation":[{"name":"Clinical Trial Research Center Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing 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