Estrobolome: Is there a missing link?

Estrogens play an important role throughout a woman's life; therefore, disrupting their physiological production will alter hormonal balance with consequences for estrogen-related conditions, such as endometriosis and adenomyosis. The gut microbiome (GM) plays a critical role in regulating systemic estrogen concentrations, since a number of microorganisms present in the GM possess the enzyme β-glucuronidase (β-GLC), a key factor in regulating host estrogen metabolism. Although most studies have focused on the conversion of estrogen glucuronides to active estrogens by β-GLC in gut bacteria, it is known that the GM also contains steroid sulfatases (STS), which are able to convert inactive sulfated estrogens to active ones. This is especially important because estrone (E1) sulfate (E1S) is quantitatively the most important estrogen in the human and can be readily converted to E1 and estradiol (E2). It has been shown that estrogen sulfates are present in bile and can therefore reach the intestines, raising the possibility of biologically active E1 and E2 formation in the intestine by bacterial enzyme transformation. Everything depends on the presence of sulfatases in the GM, and in this respect, STS have been found in a variety of microbial species. This means that sulfatases are poised to reactivate estrogens, which are then capable of undergoing enterohepatic recirculation and exerting systemic effects throughout the body. Given that estrogen sulfates represent the largest component of circulating estrogens that are secreted by the liver into the intestines via the bile, the role of gut microbial sulfatases may be superior to that of β-GLC.