There seems to be more than one source of male steroid hormones in the body: and to be precise, certain gut bacteria can be a source of male steroid hormones. In an article published in the Journal of Lipid Research, researchers show that a bacterial species converts glucocorticoids into androgens, a group of male steroid hormones. The implication is that the endocrine system may not be the only source of androgens and other regulatory molecules: the intestinal microbiota, in fact, could represent another one. Phillip Hylemon of Virginia Commonwealth University explains that since the 1960s there is evidence that secondary bile acids, which are microbial products produced by primary bile acids secreted by the gall bladder, are related to cholesterol gallstones. These are positively associated with intestinal colic and acute pancreatitis in case of bile duct occlusion. Furthermore, the altered metabolism of bile salts by the intestinal bacterial flora seems to positively associate with colon cancer.
The research team elaborated on the way in which the bacterium Clostridium scindens carries out the hormonal transformation of bile acid. But it turns out that C. scindens can modify glucocorticoids and convert them to androgens. Why is this important? Hylemon explains that, in the gut, androgen steroids can be further modified by other members of the intestinal microbiota to produce testosterone derivatives. It is then possible that these steroid metabolites interact with the host nuclear receptors or other intestinal organisms. In males, for example, the prostate gland is close to the wall of the rectum. Therefore, androgens produced by intestinal bacteria are able to passively pass, possibly altering the physiology of prostate cells. And this could represent a mechanism that hides beneath the appearance of benign prostatic hypertrophy as we age. C. scindens is the only bacterium in the human gastrointestinal tract so far identified to do this, but how does it convert the glucocorticoids into androgens?
Hylemon and colleagues used high-speed nucleic acid sequences to identify the genes encoding the enzymes involved in this biotransformation. They knew that genes were activated by cortisol, a steroid hormone induced by stress. By comparing the levels of messenger RNA (mRNA) of C. scindens grown in liquid culture with and without cortisol, investigators reasoned that they would be able to identify candidate genes. They identified a group of genes encoding a trans-ketolase enzyme that is different from those involved in sugar metabolism. But the researchers still do not know if this bacterial enzyme has evolved specifically to carry out the bio-transformation of glucocorticoids into androgens. The implication of the work is that C. scindens could play an important role in the endocrine system. Doctors Hylemon and Ridlon comment: “It is generally recognized in the field that the intestinal microbiota is a virtual organ, and we believe that, like other organs of the body, this organ has specialized cells that produce hormones derived from bile acids synthesized by the host and steroid hormones.
Because the intestinal microbiota is able to produce hormones, there are no more doubts: the gut microbiota is an endocrine organ. “The research team would now like to investigate whether these androgen-like molecules have the same effects. on the physiology of those generated by the human endocrine system, Hylemon says: “Our next step is to screen bile acids and the metabolites of steroid hormones generated by bacteria. In fact, they can bind and activate both surface receptors and nuclear receptors, being able to generate confusion on the interpretation of responses”. The results of this study have enormous implications on the connections between human health and the immune system. If it is true that certain intestinal bacteria can contribute to the synthesis of steroid hormones, one could understand why certain diseases are more frequent in one sex than in the other. E.g. autoimmune diseases such as rheumatoid arthritis, systemic lupus and multiple sclerosis, have a significantly higher incidence among women than men, What does this depend on the differences in composition between the human intestine and the woman? This hypothesis has been described, but not detailed. Is it possible that C. scindens preferably colonizes the male intestine with respect to the female one?
To complicate matters, the team’s study found that the bacterium Propionimicrobium lymphophilum, a normal colonizer of the urinary tract, also expresses an almost identical enzyme (17,20-desmolase). What is the meaning of this phenomenon? Let the confirmations and answers come from the experts.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Tetel MJ et al. J Neuroendocrinol. 2017; Oct 12.
Devendran S, Ridlon JM et al. J Lipid Res. 2017; 58(5):916-925.
Moreno-Indias I et al. Endocrinology. 2016; 157(12):4888-4898.
Ortona E et al. Ann Ist Super Sanita. 2016 Apr-Jun; 52(2):205-12.
Markle JG et al. Science. 2013 Mar 1; 339(6123):1084-88.