{"title":"Mechanistic insights into endometriosis: roles of Streptococcus agalactiae and L-carnitine in lesion development and angiogenesis.","authors":"Yuan Zhuang, Ting Lyu, Yang Chen, Wei Li, Lei Tang, Shi-Ping Xian, Peng-Fei Yang, Lijie Wang, Qian-Qian Zhang, Chaoming Mei, Yu-Jing Lin, Zhixiang Yan, Zhanyu Li, Jian-Zhong He, Fa-Min Zeng","doi":"10.1007/s10456-025-09991-7","DOIUrl":null,"url":null,"abstract":"<p><p>Retrograde menstruation is a widely recognized etiological factor for endometriosis (EMs); however, it is not the sole cause, as not all affected women develop EMs. Emerging evidence suggests a significant association between the vaginal microbiota and EMs. Nonetheless, the precise mechanisms by which microbial communities influence the pathophysiology and progression of EMs remain unclear. In this study, the cervical mucus from patients with EMs showed significantly greater microbial abundance compared with that of controls, with Streptococcus agalactiae (S. agalactiae) exhibiting the most substantial increase as determined by 16S rRNA gene sequencing. In a murine model, elevated S. agalactiae levels significantly increased the lesion number and colonization, whereas antibiotic treatment reduced lesion formation. Metabolomic analyses showed elevated L-carnitine levels in the cervical secretions and serum of patients with EMs, a finding corroborated in murine tissues. Exogenous L-carnitine administration similarly increased the number and weight of endometriotic lesions. Meanwhile, the inhibition of L-carnitine synthesis suppressed lesion formation induced by S. agalactiae. In vitro, both S. agalactiae and L-carnitine promoted EMs cell proliferation, migration, and invasion. L-carnitine synthesis inhibition attenuated cell motility stimulated by S. agalactiae. Mechanistically, S. agalactiae enhanced angiogenesis through L-carnitine by upregulating vascular endothelial growth factor expression and increasing human umbilical vein endothelial cell motility. These findings identify S. agalactiae as a key cervical microbiome component in EMs development and reveal a microbiota-metabolite-angiogenesis axis that may offer novel therapeutic targets.</p>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"28 3","pages":"38"},"PeriodicalIF":9.2000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198069/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angiogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10456-025-09991-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
Abstract
Retrograde menstruation is a widely recognized etiological factor for endometriosis (EMs); however, it is not the sole cause, as not all affected women develop EMs. Emerging evidence suggests a significant association between the vaginal microbiota and EMs. Nonetheless, the precise mechanisms by which microbial communities influence the pathophysiology and progression of EMs remain unclear. In this study, the cervical mucus from patients with EMs showed significantly greater microbial abundance compared with that of controls, with Streptococcus agalactiae (S. agalactiae) exhibiting the most substantial increase as determined by 16S rRNA gene sequencing. In a murine model, elevated S. agalactiae levels significantly increased the lesion number and colonization, whereas antibiotic treatment reduced lesion formation. Metabolomic analyses showed elevated L-carnitine levels in the cervical secretions and serum of patients with EMs, a finding corroborated in murine tissues. Exogenous L-carnitine administration similarly increased the number and weight of endometriotic lesions. Meanwhile, the inhibition of L-carnitine synthesis suppressed lesion formation induced by S. agalactiae. In vitro, both S. agalactiae and L-carnitine promoted EMs cell proliferation, migration, and invasion. L-carnitine synthesis inhibition attenuated cell motility stimulated by S. agalactiae. Mechanistically, S. agalactiae enhanced angiogenesis through L-carnitine by upregulating vascular endothelial growth factor expression and increasing human umbilical vein endothelial cell motility. These findings identify S. agalactiae as a key cervical microbiome component in EMs development and reveal a microbiota-metabolite-angiogenesis axis that may offer novel therapeutic targets.
期刊介绍:
Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.