The Healthy Female Microbiome Across Body Sites: Effect of Hormonal Contraceptives and the Menstrual Cycle

Abstract

Background: There is increasing evidence that the vaginal microbiome influences women’s health. V agina l dysbiosis with a low abundance of L actobacillus h as been connected to gynaecological and obstetric complications. However, the interplay between the vaginal microbiome and the microbiome in other body sites is not yet described. In addition, fluctuating endogenous sex hormones may exert an effect on microbiome composition and are markedly changed by hormonal contraception . This study includes a cohort of 160 healthy young Caucasian women using three different contraceptive regimens: non-hormonal methods, combined oral contraceptive (COC) or levonorgestrel intra-uterine system (LNG-IUS ) . The oral, vaginal, rectal and faecal microbiome s are characterized by shot gun sequencing during each phase of the menstrual cycle (menses, follicular and luteal phases). Results: The use of COC and LNG-IUS do not affect the microbiome composition or diversity . However , an increased diversity in the vaginal microbiome is observed during menses , followed by a subsequent expansion of Lactobacillus during the follicular and luteal phase s which correlate s with measured serum oestradiol levels (r = 0.11, p<0.001) . During menses 89 women (58%) ha ve a dysbiotic vaginal microbiome with less than 60% Lactobacillus spp . This decline s to 49 (32%) in the follicular phase (p = 1.3E-5) and 44 (29%) in the luteal phase (p = 4.6E-7) . During menses, bacterial richness and diversity in saliva reach its lowest while no difference is observed in the faecal microbiome . T he microbiome in different body sites is on average more similar within the same individual than between individuals , despite phase or hormonal treatment . Only the vagina present s a clear cluster structure with dominance of either Lactobacillus crispatus , Lactobacillus iners , Gardnerella vaginalis or Prevotella spp. Conclusions: The use of COC or LNG-IUS is not associated with changes of the healthy female microbiome except for increased stability in the vagina in LNG-IUS users . Body site is the main driver of the microbiome, including a clear difference between faecal and rectal samples. The menstrual cycle is a confounding factor for microbiome composition in both saliva and the vagina and should be considered when analysing the microbiome in women of reproductive age.

Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls

“…Different microbiota characteristics are observed in women at different physiological stages [30] . In healthy women of reproductive age, the vaginal microbiome composition changes dramatically before and after menstruation [31] . Menstrual blood owing through the vagina leaves su cient iron for pathogens, and the iron necessary for pathogen metabolism [32] , which is reduced by the iron-binding a nity of lactoferrin, is replenished.…”

“…Additionally, studies measuring estradiol levels and vaginal microbiome composition in women who use oral contraceptives to inhibit ovulation have shown that the high diversity observed during menstruation is mainly driven by estradiol withdrawal before menstruation rather than by the dynamic drive of progesterone. Lactobacillus abundance increases during the follicular and luteal phases, gradually normalizing the vaginal microecology [31,33] . Under the in uence of this periodicity, combined with our test results, we found different types of dominant bacterial pro les in patients with adenomyosis in both the both luteal and follicular stages, which provided a reference for the detection of biomarkers in patients with speci c menstrual cycles or to evaluate their e cacy.…”

Vaginal microbial dynamics and pathogen colonization in a humanized microbiota mouse model

“…Lactobacillus relative abundance during menses (51)(52)(53)(54)(55)(56). To determine if the HMb mice vaginal microbiota is influenced by estrous stage, five HMb mice were swabbed daily for one week.…”