Figure 2.

Known microbial transformation on estrogens and androgens. The degree of enterohepatic recirculation of two forms of endogenous estrogens varies greatly among host species [143]. However, estriol exhibits significant enterohepatic recycling. Conjugation of estrogens with sulfate and glucuronide occurs largely in liver, resulting in compounds such as estriol-3-sulfate-16-glucuronide (E3-3-S-16-G). This conjugated estrogenic metabolite is then subjected to excretion via the intestinal tract. Gut microbial sulfatases can hydrolyze E3-3-S-16-G to E3-16-G, which can return to the liver for excretion or reconjugation or be hydrolyzed further into free E3 by bacterial β-glucuronidase for reabsorption. Gut microbes can also reconjugate free E3 into E3-3-G, which is then subjected to excretion. Moreover, in vitro studies suggest that gut microbes are able to convert estrone into estradiol (aerobically and anaerobically), as well as 16-α-hydroxyestrone into estriol, but this reaction has only been shown to occur in the presence of oxygen [50]. Similarly, conjugated androgens can be hydrolyzed in the intestinal tract via bacterial β-glucuronidase into free androgens for reabsorption. Further, glucocorticoids can be converted it into androgens via side-chain cleaving capacity of bacterial desABCD-encoded enzymes.