Approaching menopause? Know how your gut microbiome can help or hinder


 

 

Most women are wary of “that certain age” when their estrogen levels begin to drop.

The hormone estrogen is of utmost importance in the human body. It regulates glucose and lipid metabolism, fat deposition, adipocyte (fat cell) differentiation, female reproductive functions, bone turnover, cardiovascular health, and cell replication. 

Low levels of estrogen in post-menopausal women can have an adverse effect on a large number of physiological processes, which has clinical implications downstream: gynecological issues may manifest; in addition, brain cognition and gut health may be affected. 

Research has begun to unravel the connection between the gut microbiome and the levels of estrogen circulating in the body, also referred to as the estrogen-gut microbiome axis. The gut microbiome plays a major role in the regulation of estrogen levels. As a result, gut dysbiosis increases the risk of developing estrogen-related diseases such as breast cancer, in addition to PCOS (polycystic ovary syndrome) and endometriosis. 

The “Estrobolome” and its workings

The estrobolome is defined as the “gene repertoire of the gut microbiota that is capable of metabolizing estrogens.” The bacterial species that produce enzymes that are active in estrogen deconjugation and conjugation, namely,  β(beta)-glucuronidases and β-glucuronides, are of the utmost importance as they modulate estrogen activity. Beta-glucuronidase activity produces active, unbound (a.k.a free or deconjugated) estrogen that is capable of binding to estrogen receptors and influencing estrogen-dependent physiological processes. 

Furthermore, the estrobolome is thought to impact estrogen metabolism by modulating the enterohepatic circulation of estrogens, thus affecting circulating and excreted estrogen levels.

In a healthy gut microbiome, the amount of beta-glucuronidase produced by the estrobolome is optimal to maintain estrogen homeostasis. Gut dysbiosis alters beta-glucuronidase activity in a manner that results in either insufficient or excessive levels of free estrogen, resulting in the onset of estrogen-driven pathologies, including obesity, metabolic syndrome, cardiovascular disease (CVD), and fertility issues. 

The drop in estrogen levels at menopause is normal. However, if gut dysbiosis is also present, any decrease in beta-glucuronidase activity it causes may make things worse, by increasing the risk of these chronic diseases. 

Factors that influence the Estrobolome

Since the estrobolome is a subset of our gut microbiome, what we eat affects it, too. All the diet and lifestyle factors that disrupt the microbiota can potentially disrupt the estrobolome. In addition, antibiotics and hormonal contraceptives alter both the gut microbiota and estrogen levels in the body, adversely impacting the estrobolome. 

Dietary phytoestrogens, pre- and probiotics

The debate on the health benefits versus adverse effects of phytoestrogens is ongoing and hitherto inconclusive. Phytoestrogens are plant-derived dietary compounds with structural similarity to 17-β-oestradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti) oestrogenic effects by binding to the oestrogen receptors.

The beneficial health effects of phytoestrogens include:

  • A lowered risk of menopausal symptoms like hot flushes
  • Lowered risk of obesity, CVD, metabolic syndrome, and type-2 diabetes and cancer
  • Lowered risk of Brain function disorders

On the other hand, the (anti)oestrogenic properties of phytoestrogens, with their potential to act as endocrine disruptors and cause adverse health effects has raised several red flags.

Pre- and probiotics known to benefit the gut microbiome are also being explored in the context of benefiting the bacterial species-specific to the estrobolome. Targeting the gut bacteria that have beta-glucuronidase activity in an effort to decrease estrogen-related cancer risk, or to develop future therapies, presents an attractive avenue of research. 

All in all, the estrobolome is now recognized as a vital subset of the gut microbiota. The estrobolome and the therapies that can modulate its function for the better may present an attractive diagnostic and therapeutic target in the area of women’s health.

Author: Ranjan Sinha