Trends in Endocrinology & Metabolism
ReviewGut and vaginal microbiomes on steroids: implications for women’s health
Section snippets
Estrobolome and the GM
The estrobolome describes the functional collection of all enteric bacterial gene products capable of metabolizing estrogens (Figure 2). In the process of conjugation, estrogens are metabolized in the liver and marked for excretion via urine and feces by the addition of a glucuronic acid moiety [7]. Removal of the glucuronic acid group via deconjugation allows estrogens to remain in the body and exert their effects. Enteric bacteria (e.g., the genera Bifidobacterium, Clostridium, and
Menstrual cycle
E2 and progesterone levels fluctuate across different phases of the menstrual cycle (Figure 1A). The follicular phase is characterized by rising estrogen levels, in particular E2. During the ovulatory phase, E2 peaks when progesterone levels also begin to rise. During the luteal phase the follicle transforms into the corpus which secretes progesterone for stimulation of the secretory endometrium. When pregnancy does not occur, the corpus luteum degenerates and estrogen and progesterone decline
Pregnancy
Endometrial receptivity is guided by progesterone production during the luteal phase. During implantation, progesterone and estrogens regulate important physiologic mechanisms in preparation for embryonic development [57]. Estrogen and progesterone levels increase throughout pregnancy, peak during the third trimester [58], and return to pre-pregnancy values by 5 days postpartum [59] (Figure 1C).
Menopause
Menopause is defined by the permanent cessation of ovarian follicle activity and the lack of a menstrual cycle for 1 year, marking the end of natural reproductive life in women [88]. The period of decline in ovarian function is termed perimenopause and is characterized by increases in follicle-stimulating hormone owing to the lack of follicles and negative feedback from the ovaries [88]. As ovarian activity continues to decrease, the production of E2 and progesterone ceases (Figure 1E). At
Concluding remarks
The interaction between sex steroids and the vaginal and gut microbiomes is a bidirectional axis that profoundly impacts on women’s health across all life stages. The GM modulates circulating estrogens in the estrobolome, and in turn these circulating estrogens help to shape the VM, driving reproductive tract health. The gut and vaginal microbiomes appear to have crucial overlapping functions in various disease states in women’s health. However, there are glaring gaps in our understanding of
Acknowledgments
This work was supported, in part, by Clinical and Translational Science Award (CTSA) grant KL2 TR002379 from the National Center for Advancing Translational Science and a career enhancement award from the National Institutes of Health (NIH; grant P50 CA136393) to M.R.S.W-A., and by Wellesley College Jenkins Distinguished Chair in Neuroscience Funds (to M.J.T.).
Declaration of interests
The Mayo Foundation for Medical Education and Research (inventor M.R.S.W-A.) has been issued a patent 'Methods and Materials for Treating Endometrial Cancer', US10072303B2. The content of the patent relates to the use of the microbiome to address endometrial cancer. M.R.S.W-A. is a member of the scientific advisory board of LUCA Biologics Inc. on research related to urinary tract infections, preterm birth, and reproductive medicine. The other authors declare no conflicts of interest.
Glossary
- Bacterial vaginosis (BV)
- a state of perturbed bacterial composition in the vagina, often leading to inflammation.
- Estradiol (E2)
- a major ovarian estrogen steroid hormone.
- Gestational diabetes (GD)
- the onset of diabetes in pregnancy.
- Gut microbiota (GM)
- commensal microbes in the gastrointestinal tract, whereas the gut microbiome constitutes all microbes and their associated gene products.
- Hypothalamus–pituitary–adrenal (HPA) axis
- the primary neuroendocrine pathway comprising the hypothalamus, anterior
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Equal contributions