The gut microbiota is a major regulator of androgen metabolism in intestinal contents

Abstract

Androgens exert important effects both in androgen-responsive tissues and in the intestinal tract. To determine the impact of the gut microbiota (GM) on intestinal androgen metabolism, we measured unconjugated (free) and glucuronidated androgen levels in intestinal contents from the small intestine, with a low bacterial density, and from cecum and colon, with a high bacterial density. Using a specific, sensitive gas chromatography-tandem mass spectrometry method, we detected high levels of glucuronidated testosterone (T) and dihydrotestosterone (DHT) in small intestinal content of mice of both sexes, whereas in the distal intestine we observed remarkably high levels of free DHT, exceeding serum levels by >20-fold. Similarly, in young adult men high levels of unconjugated DHT, >70-fold higher than in serum, were detected in feces. In contrast to mice with a normal GM composition, germ-free mice had high levels of glucuronidated T and DHT, but very low free DHT levels, in the distal intestine. These findings demonstrate that the GM is involved in intestinal metabolism and deglucuronidation of DHT and T, resulting in extremely high free levels of the most potent androgen, DHT, in the colonic content of young and healthy mice and men.

Relationship between gut environment, feces-to-food ratio, and androgen deficiency-induced metabolic disorders

“…Some gut microbiota regulate androgen levels in the intestine by deglucuronidation to release free dihydrotestosterone from its glucuronide conjugates. 41 This also demonstrates the ability of gut microbiota to regulate androgen levels through different mechanisms. 41 Conversely, bacterial–host interactions can also be regulated by androgen levels.…”

“… 41 This also demonstrates the ability of gut microbiota to regulate androgen levels through different mechanisms. 41 Conversely, bacterial–host interactions can also be regulated by androgen levels. 26 , 42 , 43 …”

Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis

“…Interestingly, androgens also play a central role in sexual physiology, and disturbances in their action are associated with the development of different conditions in both men and women. Collden et al (2019) demonstrated that glucuronidases produced by the cecal microbiota can degrade the high content of testosterone and dihydrotestosterone found in the small intestine. The high content of free or unconjugated dihydrotestosterone found in the colon of healthy young mice of both sexes and men suggests that gut microbiota might be involved in the metabolism of intestinal androgens and can therefore affect the risk of androgen-related diseases in the distal intestine and probably also in remote anatomical sites.…”

Crosstalk between circadian rhythms and the microbiota

“…In both mice and humans, androgens modulate the gut microbiota composition. 31,[63][64][65] Interestingly, mouse studies showed that the gut microbiota modulate androgen metabolism, 66 suggesting two-way crosstalk. Androgens also modulate microbial oscillations.…”