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However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P\u2009&lt;\u20090.05). Patients with VLS had a higher abundance of<jats:italic>Enterobacter cloacae<\/jats:italic>,<jats:italic>Flavobacterium_branchiophilum<\/jats:italic>,<jats:italic>Mediterranea_sp._An20, Parabacteroides_johnsonii<\/jats:italic>and<jats:italic>Streptococcus_bovimastitidis<\/jats:italic>on the vulvar skin, while<jats:italic>Corynebacterium_sp._zg-913<\/jats:italic>was less abundant compared to the control group. The relative abundance of<jats:italic>Sphingomonas_sp._SCN_67_18<\/jats:italic>,<jats:italic>Sphingobium_sp._Ant17,<\/jats:italic>and<jats:italic>Pontibacter_sp_BT213<\/jats:italic>was significantly higher in the gut samples of patients with VLS.<jats:italic>Paenibacillus_popilliae<\/jats:italic>,<jats:italic>Gemella_asaccharolytica<\/jats:italic>, and<jats:italic>Coriobacteriales_bacterium_DNF00809<\/jats:italic>compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of<jats:italic>Bacteroidales_bacterium_43_8<\/jats:italic>,<jats:italic>Bacteroides_sp._CAG:20<\/jats:italic>,<jats:italic>Blautia_sp._AM28-10, Fibrobacter_sp<\/jats:italic>._<jats:italic>UWB16<\/jats:italic>,<jats:italic>Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79<\/jats:italic>, and<jats:italic>Tolumonas_sp<\/jats:italic>. Additionally, the<jats:italic>butyrate-producing bacterium SS3\/4<\/jats:italic>showed a significant difference compared to the controls. The study found a negative relationship between<jats:italic>Sphingobium_sp._Ant17<\/jats:italic>in stool and Skindex-16 (P\u2009&lt;\u20090.05), while<jats:italic>Mediterranea_sp._An20<\/jats:italic>had a positive correlation with Skindex-16 (P\u2009&lt;\u20090.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.<\/jats:p>","DOI":"10.1038\/s41598-024-58983-y","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T16:01:48Z","timestamp":1712764908000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Alternations in the human skin, gut and vaginal microbiomes in perimenopausal or postmenopausal Vulvar lichen sclerosus"],"prefix":"10.1038","volume":"14","author":[{"given":"Xiaolei","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangdong","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangwen","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"issue":"8","key":"58983_CR1","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1158\/1055-9965.EPI-16-0019","volume":"25","author":"MC Bleeker","year":"2016","unstructured":"Bleeker, M. 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