Lee S, Aasmets O, Arffman R K, Laru J, Rossi H R, Salumets A, Piltonen T T, Org E
Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.
Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Hum Reprod. 2025 Mar 1;40(3):518-528. doi: 10.1093/humrep/deae270.
Do polycystic ovary syndrome (PCOS), menstrual cycle phases, and ovulatory status affect reproductive tract (RT) microbiome profiles?
We identified microbial features associated with menstrual cycle phases in the upper and lower RT microbiome, but only two specific differences in the upper RT according to PCOS status.
The vaginal and uterine microbiome profiles vary throughout the menstrual cycle. Studies have reported alterations in the vaginal microbiome among women diagnosed with PCOS.
STUDY DESIGN, SIZE, DURATION: This prospective case-control study included a cohort of 37 healthy control women and 52 women diagnosed with PCOS. Microbiome samples were collected from the vagina as vaginal swabs (VS) and from the uterus as endometrial flushing (EF) aspirate samples, and compared according to PCOS diagnosis, the menstrual cycle phases, and ovulatory status, at Oulu University Hospital (Oulu, Finland) from January 2017 to March 2020.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 83 VS samples and 80 EF samples were collected. Age and body mass index (BMI) were matched between women with and without PCOS. Clinical characteristics were assessed using blood samples collected between cycle days 2 and 8, and microbial DNA was sequenced on the Ion Torrent platform. Microbial alpha diversity (i.e. the observed number of unique genera and Shannon diversity index) was analysed across sample types, PCOS diagnosis and menstrual cycle phases. Linear mixed-effects models were utilised to identify microbial features in relation to PCOS and the menstrual cycle phases. Associations between the beta diversity of the RT microbiome and PCOS- and cycle-related clinical features were calculated using PERMANOVA.
Microbial alpha diversity showed no difference with PCOS (VS: Pobserved feature = 0.836, Pshannon = 0.998; EF: Pobserved feature = 0.366, Pshannon = 0.185), but varied with menstrual cycle phases (VS: Pobserved feature = 0.001, Pshannon = 0.882; EF: Pobserved feature = 0.026, Pshannon = 0.048). No difference was observed in beta diversity based on either PCOS or the menstrual cycle phases (VS: PPCOS = 0.280, Pcycle = 0.115; EF: PPCOS = 0.234, Pcycle = 0.088). In the endometrial flushing samples, we identified two novel microbial features, characterised by the ratio of differential abundance of two genera, associated with PCOS (FDR ≤ 0.1) and 13 novel features associated with the menstrual cycle phases (FDR ≤ 0.1).
LIMITATIONS, REASONS FOR CAUTION: Although this was the first study to simultaneously analyse, the lower and upper RT microbiome in women with and without PCOS, the limited sample size of anovulatory cases may hinder the detection of differences related to PCOS and ovulatory status.
The main finding suggests that PCOS and the menstrual cycle phases are associated with specific microbial features in the upper RT, indicating that the analysis of the upper RT microbiome can potentially identify biomarkers for both PCOS and menstrual cycle phases.
STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Research Council of Finland (grants no. 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (grant no. NNF21OC0070372), and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (MATER, grant no. 813707). This research was also funded by the Estonian Research Council (grants no. PRG1076, PRG1414), the Horizon Europe grant (NESTOR, grant no. 101120075) of the European Commission, and EMBO Installation Grant (grant no. 3573). The funders did not participate in any processes of the study. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
N/A.
多囊卵巢综合征（PCOS）、月经周期阶段和排卵状态是否会影响生殖道（RT）微生物组谱？
我们在上下生殖道微生物组中确定了与月经周期阶段相关的微生物特征，但根据PCOS状态，上生殖道仅存在两个特定差异。
阴道和子宫微生物组谱在整个月经周期中会有所变化。研究报告称，被诊断为PCOS的女性阴道微生物组存在改变。
研究设计、规模、持续时间：这项前瞻性病例对照研究纳入了37名健康对照女性和52名被诊断为PCOS的女性。于2017年1月至2020年3月在奥卢大学医院（芬兰奥卢）收集微生物组样本，从阴道采集阴道拭子（VS）样本，从子宫采集子宫内膜冲洗液（EF）抽吸样本，并根据PCOS诊断、月经周期阶段和排卵状态进行比较。
参与者/材料、地点、方法：共收集了83份VS样本和80份EF样本。PCOS患者和非PCOS患者的年龄和体重指数（BMI）相匹配。使用在月经周期第2至8天采集的血液样本评估临床特征，并在Ion Torrent平台上对微生物DNA进行测序。分析了不同样本类型、PCOS诊断和月经周期阶段的微生物α多样性（即观察到的独特属数量和香农多样性指数）。利用线性混合效应模型确定与PCOS和月经周期阶段相关的微生物特征。使用PERMANOVA计算生殖道微生物组β多样性与PCOS及周期相关临床特征之间的关联。
微生物α多样性在PCOS患者中无差异（VS：P观察到的特征 = 0.836，P香农 = 0.998；EF：P观察到的特征 = 0.366，P香农 = 0.185），但随月经周期阶段而变化（VS：P观察到的特征 = 0.001，P香农 = 0.882；EF：P观察到的特征 = 0.026，P香农 = 0.048）。基于PCOS或月经周期阶段的β多样性均未观察到差异（VS：P PCOS = 0.280，P周期 = 0.115；EF：P PCOS = 0.234，P周期 = 0.088）。在子宫内膜冲洗液样本中，我们确定了两个新的微生物特征，以两个属的差异丰度比为特征，与PCOS相关（FDR≤0.1），以及13个与月经周期阶段相关的新特征（FDR≤0.1）。
局限性、注意事项：尽管这是第一项同时分析有或无PCOS女性的下生殖道和上生殖道微生物组的研究，但无排卵病例的样本量有限可能会妨碍检测与PCOS和排卵状态相关的差异。
主要研究结果表明，PCOS和月经周期阶段与上生殖道的特定微生物特征相关，这表明对上生殖道微生物组的分析可能潜在地识别出PCOS和月经周期阶段的生物标志物。
研究资金/利益冲突：本研究由芬兰研究理事会（资助编号315921、321763、336449）、西格丽德·尤塞利乌斯基金会、诺和诺德基金会（资助编号NNF21OC0070372）以及欧盟“地平线2020”研究与创新计划下的玛丽·居里奖学金（MATER，资助编号813707）资助。本研究还由爱沙尼亚研究理事会（资助编号PRG1076、PRG1414）、欧盟委员会的“地平线欧洲”资助（NESTOR，资助编号101120075）以及EMBO入职资助（资助编号3573）资助。资助者未参与研究的任何过程。作者声明，该研究是在没有任何可能被视为潜在利益冲突的商业或财务关系的情况下进行的。
无。
