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In women, vulvar lichen sclerosus presents with a wide range of clinical features, including pruritus, erythema, burning, pain, dysuria, architectural distortion, scarring, and the formation of ivory-white atrophic plaques. While the precise etiology of LSc remains unclear, increasing evidence indicates that prolonged exposure to urine and occlusion may play a central role in its pathogenesis. Additionally, the role of the genital microbiome has garnered increasing attention, with dysbiosis\u2014an imbalance in microbial communities\u2014emerging as a potential contributing factor. Prior investigations have reported an increased abundance of Gardnerella in women with LSc, but findings regarding Streptococcus and Lactobacillus have been inconsistent. This study aimed to investigate the relationship between the vulvar microbiome and LSc. Materials and Methods: Forty-seven women with LSc and seven healthy controls were recruited from the Division of Dermatology, Ryhov Hospital, J\u00f6nk\u00f6ping. Vulvar swabs were obtained from affected skin areas. The 16S rRNA regions were amplified and sequenced using the Illumina MiSeq system. Differential abundance analyses were conducted using four regression methods, and genera were considered significant only if identified by at least two methods. Results: Compared to controls, LSc patients showed reduced abundance of Lactobacillus, Finegoldia, Lawsonella, Stapylococcus, Cutibacterium, and an unidentified genus belonging to the Actinomycetaceae family. In contrast, Porphyromonas and Ezekiella, were significantly increased. Beta diversity analysis revealed significant differences in microbiome composition between groups (p = 0.022). Conclusions: The vulvar microbiome of women with LSc differs significantly from that of healthy controls. These findings support a possible role of microbial dysbiosis in LSc pathogenesis, highlighting the need for further research into microbiome-targeted interventions.<\/jats:p>","DOI":"10.3390\/medicina61091632","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T19:16:17Z","timestamp":1757445377000},"page":"1632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genital Lichen Sclerosus\u2014The Role of the Vulvar Microbiome"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-043X","authenticated-orcid":false,"given":"Sandra","family":"Jerkovic Gulin","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Ryhov County Hospital, 551 85 J\u00f6nk\u00f6ping, Sweden"},{"name":"Division of Cell Biology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Alml\u00f6f","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2045-7142","authenticated-orcid":false,"given":"Oliver","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Ryhov County Hospital, 551 85 J\u00f6nk\u00f6ping, Sweden"},{"name":"Division of Cell Biology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-0149","authenticated-orcid":false,"given":"Georgios","family":"Kravvas","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK"},{"name":"Department of Medicine, University College London, London WC1E 6JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippa","family":"Lundin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-4762","authenticated-orcid":false,"given":"Malin","family":"Bergman Jungestr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-7210","authenticated-orcid":false,"given":"Jan","family":"S\u00f6derman","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"},{"name":"Laboratory Medicine, Ryhov County Hospital, 551 85 J\u00f6nk\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Luca, D.A., Papara, C., Vorobyev, A., Staiger, H., Bieber, K., Thaci, D., and Ludwig, R.J. 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