The vaginal microbiome amplifies sex hormone‐associated cyclic changes in cervicovaginal inflammation and epithelial barrier disruption

• Published in: American journal of reproductive immunology (1989) Vol. 80; no. 1; pp. e12863 - n/a
• Main Authors: Bradley, Frideborg, Birse, Kenzie, Hasselrot, Klara, Noël‐Romas, Laura, Introini, Andrea, Wefer, Hugo, Seifert, Maike, Engstrand, Lars, Tjernlund, Annelie, Broliden, Kristina, Burgener, Adam D.
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01-07-2018
• Subjects: Adolescent; Adult; Anaerobic bacteria; Community structure; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Female; female genital tract; Genital tract; Gonadal Steroid Hormones - metabolism; HIV; Human immunodeficiency virus; Humans; Inflammation; Inflammation - metabolism; Inflammation - microbiology; Lactobacillus; Leukocyte migration; Leukocytes - metabolism; Leukocytes - microbiology; Mass spectroscopy; Medicin och hälsovetenskap; Menstrual cycle; Menstrual Cycle - metabolism; Menstruation; microbiome; Microbiomes; Microbiota - physiology; Mucosa; Neutrophils; Neutrophils - metabolism; Neutrophils - microbiology; Ovulation; Ovulation - metabolism; Proteome - metabolism; Proteomes; rRNA 16S; Secretions; Sex hormones; Structure-function relationships; Sweden; Vagina; Vagina - metabolism; Vagina - microbiology; vaginal inflammation; Young Adult; Sweden; vaginal inflammation; female genital tract; HIV; sex hormones; microbiome; menstrual cycle
• ISSN: 1046-7408; 1600-0897; 1600-0897
• DOI: 10.1111/aji.12863

Problem
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.
Method of study
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.
Results
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.
Conclusion
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.