The gut microbiome — a complex ecosystem of bacteria, viruses, fungi, and protozoa — plays a critical role in endocrine and reproductive function. Increasingly viewed as an endocrine organ, the gut microbiota influence hormone metabolism and affect distal organs and associated biological pathways.1
Research suggests a bidirectional “gut microbiota-gonadal axis,” where gut microbial homeostasis is essential for reproductive health.1,2 Disruptions to the gut microbiota, or dysbiosis, can result in reproductive pathologies, such as pregnancy complications and outcomes, and associated conditions, including endometriosis, polycystic ovarian syndrome (PCOS), and gynecologic cancers.1
Although there is lack of conclusive data regarding the influence of the gut microbiota on female reproduction, understanding this association will improve reproductive outcomes and overall well-being in women.2
We received insights from Brandilyn A. Peters-Samuelson, PhD, and Ramakrishna Kommagani, PhD, who spoke in detail about the relationship between the gut microbiome, women’s health conditions, such as endometriosis, and the female reproductive system.
Providers must discuss the importance of a healthy gut to improve overall health of women.
Dr Peters-Samuelson is an associate professor in the Department of Epidemiology and Population Health (Epidemiology) at Albert Einstein College of Medicine, New York.
Dr Kommagani is an associate professor at the Department of Pathology and Immunology and Department of Molecular Virology and Microbiology at Baylor College of Medicine in Houston, Texas.
Dr Peters-Samuelson: The gut microbiota may be able to “recycle” estrogens and other sex hormones through a specific metabolic process called deconjugation, which saves estrogens from fecal excretion by allowing them to be reabsorbed from the gut into the bloodstream. The gut microbiota carrying out this metabolism have been called the “estrobolome” because of their estrogen recycling activity. Because of these interactions, studies have found positive associations between gut microbiome diversity and specific “estrobolome” species with serum levels of estrogens.3 In theory, gut microbiota play an important role in women’s reproductive health by modulating estrogen levels, but more research is needed to show these relationships in human studies.
Dr Kommagani: It is known that womenwith certain gynecologic pathologies, such as endometriosis, may have changes in their gut microbiota or alterations in the gut bacterial composition.4 Research in the PCOS space has also shown altered gut bacteria in this condition, along with a role in disease progression itself.5 Although there is a bidirectional relationship, we don’t know which starts first.
In women with endometriosis, for example, gut bacteria are altered. When our group analyzed stool samples of these women, we found [that] dysbiosis and that altered bacteria are causal for endometriosis. From our studies, we observed the impact of gut microbiota on the female reproductive system, with pathologies through specific metabolites released by the bacteria. Some of these metabolites appear to promote inflammation, proliferation, and other biological processes that may result in disease progression.6
[As Dr Peters-Samuelson noted], the female reproductive system can also have an impact on gut microbiota. In endometriosis, it is believed that hyperinflammation in the peritoneum has an impact on gut physiology, thereby changing the gut microbiota. In PCOS, as well, systemic metabolic alterations may impact the gut microbiota.4,5
What is the impact of gut dysbiosis on women’s fertility, especially among women with conditions like endometriosis and PCOS?
Dr Kommagani: The direct relationship between the gut microbiome/dysbiosis and endometriosis is well-established now.4 But to what extent that affects fertility is still unclear. Not all women with endometriosis have fertility issues. There is no concrete evidence, but from an anecdotal point-of-view, if there is gut dysbiosis and one of the hallmarks of the disease is inflammation and infertility, there is probably a connection between the gut microbiome and fertility.
Disruptions in the vaginal microbiome have also been linked to impaired oocyte quality and reduced fertility, with implications extending to assisted reproductive technologies, such as in vitro fertilization (IVF).7 What can you tell us about this association?
Dr Kommagani: Evidence points to the fact that [an] infection in the vagina alters bacterial composition, which, in turn, has an impact on fertility. The vaginal microbiome profiles of healthy women with preterm pregnancies, women who are unable to get pregnant, and those with recurrent pregnancy loss, show alterations in the microbiota. A stable vaginal microbiome will support the endometrium function. An infection in the vagina will also likely affect the upper reproductive tract and the ability of the endometrium to accept and nurture embryonic growth in procedures like IVF.7,8
Can microbiome-targeted therapies be considered to improve reproductive outcomes? What is known about the effectiveness of this therapeutic approach?
Dr Kommagani: There are currently no accepted or preclinical trials employing microbiome-based therapies specifically for endometriosis or PCOS. However, fecal microbiota transplantation (FMT) from a healthy donor to patients with inflammatory bowel disease (IBD), such as Crohn disease (CD), appears to slow disease progression.9 We are still in the initial stages of research for therapies to address gut microbiota and women’s reproductive health and fertility. However, with data we have, FMT may at least partially reverse dysbiosis in these cases to a normal commensal status, which could be beneficial in alleviating some disease symptoms.1
Probiotic-based therapy may be difficult to implement because we cannot rely on commercially available probiotics that are mostly of Lactobacillus origin. Each condition is specifically and uniquely affected by a specific set of bacteria, and we must identify, isolate, and understand the factors before using them for therapy.1
How can providers guide and encourage patients to optimize their gut health to enhance fertility and overall reproductive health?
Dr Kommagani: Providers must discuss the importance of a healthy gut to improve overall health of women. A healthy diet will sustain good gut microbiota, and it is beneficial. For example, our team has shown that short-chain fatty acids, which are metabolites, are derived from fiber food that bacteria use, which enables progression of endometriosis.6 Short-chain fatty acids are shown to be beneficial in gastrointestinal diseases, such as IBD and CD. Providers should discuss with women the importance of consuming fiber to maintain optimal levels of these beneficial metabolites. This can lead to enhancing overall reproductive health.
Providers also need to consider referrals to other subspecialities. For example, women with endometriosis often have bowel issues, which can lead to misdiagnosis of the primary condition. Gastroenterologists can consider referring patients to gynecologists for a consult. Given the link with conditions like endometriosis and the gut microbiota, women should be encouraged to have a balanced diet and pay attention to their gut health (eg, symptoms of constipation).
A recent report showed that women who consumed significant amounts of coffee were more predisposed to inflammatory conditions like endometriosis, which also promotes disease progression.10 Providers can offer these resources to patients who can then develop dietary habits by shared decision-making.
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