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健康女性与多囊卵巢综合征女性阴道微生物组的比较分析:一项大型横断面研究。

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

机构信息

Center for Reproductive Medicine, Shandong University, Jinan, Shandong, 250012, China; Reproductive Medicine Center of the First Affiliated Hospital of Wenzhou Medical university, Wenzhou, 325000, Zhejiang, China.

Center for Reproductive Medicine, Shandong University, Jinan, Shandong, 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, 250012, China; Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.

出版信息

Reprod Biomed Online. 2023 Jun;46(6):1005-1016. doi: 10.1016/j.rbmo.2023.02.002. Epub 2023 Feb 10.

Abstract

RESEARCH QUESTION

What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women?

DESIGN

A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated.

RESULTS

The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25).

CONCLUSIONS

The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.

摘要

研究问题

多囊卵巢综合征(PCOS)患者与健康女性的阴道微生物组(VMB)有何不同特征?

设计

在一个单一的学术性大学附属医院进行了一项横断面研究。共招募了 1446 名参与者(PCOS 组,n=713,对照组,n=733)。使用 16S rRNA 基因测序分析阴道拭子。比较 PCOS 组和对照组之间微生物组的多样性和组成。研究了微生物相互作用网络和功能预测。

结果

PCOS 组的 alpha 多样性高于对照组(Shannon P=0.03,Simpson P=0.02),并且 PCOS 组的组内变异性更高(P<2.2E-16)。在属水平上,乳酸杆菌的比例下降(85.1%比 89.3%,假发现率 [FDR] =0.02),而阴道加德纳菌和脲原体在 PCOS 组中的比例增加(5.1%比 3.3%,FDR=0.006;1.2%比 0.6%,FDR=0.002,分别)。鉴定出嗜酸乳杆菌、普雷沃氏菌属和阴道加德纳菌为主要差异种。嗜酸乳杆菌与血清抗苗勒管激素(AMH)和甘油三酯水平呈正相关(P=2.01E-05,P=0.004,分别)。普雷沃氏菌属与 AMH 和睾酮水平呈负相关(P=0.002,P=0.003,分别)。阴道加德纳菌与 AMH、雌二醇和孕酮水平呈正相关(P=0.004,P=0.005,P=0.03,分别)。VMB 相互作用网络表明,卷曲乳杆菌、提蒙氏普雷沃氏菌和普雷沃氏菌属可能是 PCOS 组中的关键驱动因素。总体而言,在 PCOS 和对照组之间发现了 55 个差异丰度的预测基因(FDRs<0.25)。

结论

PCOS 组阴道微生物组的多样性更高,表现出更高的异质性水平。PCOS 组中乳酸杆菌的比例下降,而阴道加德纳菌和脲原体的比例增加。这些结果需要进一步研究,以验证 PCOS 与 VMB 之间的相关性。

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