Department of Medicine Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet Karolinska University Hospital, Stockholm, Sweden.
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Am J Reprod Immunol. 2018 Jul;80(1):e12863. doi: 10.1111/aji.12863. Epub 2018 Apr 30.
Susceptibility to HIV is associated with the menstrual cycle and vaginal microbiome, but their collective impact on vaginal inflammation remains unclear. Here, we characterized the cervicovaginal proteome, inflammation, and microbiome community structure and function during the menstrual cycle.
Cervicovaginal secretions were collected from regularly cycling women (n = 16) at median day 10, 16, and 24 of each menstrual cycle and analyzed by mass spectrometry, 16S rRNA gene sequencing, and a multiplex bead array immunoassay. Follicular, ovulatory, and luteal phases were defined by serum sex hormone levels.
Ovulation showed the largest mucosal proteome changes, where 30% and 19% of the 406 human proteins identified differed compared to the luteal and follicular phases, respectively. Neutrophil/leukocyte migration pathways were lowest during ovulation and peaked in the luteal phase, while antimicrobial and epithelial barrier promoting proteins were highest during ovulation. Vaginal microbial community structure and function did not vary significantly during the menstrual cycle, with the majority consistently Lactobacillus-dominant (63%) or non-Lactobacillus-dominant (25%). Fluctuations in the epithelial barrier protein RPTN between the ovulatory and luteal phase were amplified in women with Gardnerella vaginalis and anaerobic bacteria and reduced when Lactobacillus was dominant.
This small study demonstrates that sex hormones modulate neutrophil/leukocyte inflammation, barrier function, and antimicrobial pathways in the female genital tract with the strongest changes occurring during ovulation. The data further suggest a microbiome context for hormone-driven changes in vaginal immunity which may have implications for HIV susceptibility.
HIV 的易感性与月经周期和阴道微生物组有关，但它们对阴道炎症的综合影响仍不清楚。在这里，我们描述了月经周期中宫颈阴道蛋白质组、炎症和微生物组群落结构和功能。
在每个月经周期的第 10、16 和 24 天的中位数时，从定期循环的女性（n=16）中收集宫颈阴道分泌物，并通过质谱法、16S rRNA 基因测序和多重珠阵列免疫分析进行分析。卵泡期、排卵和黄体期通过血清性激素水平定义。
排卵显示出最大的黏膜蛋白质组变化，其中 406 种鉴定出的人类蛋白质中有 30%和 19%分别与黄体期和卵泡期不同。中性粒细胞/白细胞迁移途径在排卵时最低，在黄体期达到峰值，而抗菌和上皮屏障促进蛋白在排卵时最高。阴道微生物群落结构和功能在月经周期中没有显著变化，大多数情况下持续为乳杆菌主导（63%）或非乳杆菌主导（25%）。在具有阴道加德纳菌和厌氧菌的女性中，上皮屏障蛋白 RPTN 在排卵和黄体期之间的波动加剧，而当乳杆菌占优势时，这种波动会减少。
这项小型研究表明，性激素调节女性生殖道中的中性粒细胞/白细胞炎症、屏障功能和抗菌途径，排卵时变化最强。数据进一步表明，在激素驱动的阴道免疫变化中存在微生物组背景，这可能对 HIV 易感性有影响。
