How does the microbiome metabolize testosterone?

From the Guidelines

The gut microbiome plays a crucial role in testosterone metabolism, with certain bacterial species influencing testosterone levels through various mechanisms, including conversion, deconjugation, and aromatization, as evidenced by studies such as 1.

Key Mechanisms

• Certain gut bacteria, particularly those belonging to the Clostridium genus, can convert testosterone into less active metabolites through processes like 21-dehydroxylation.
• Bacteroides species can produce beta-glucuronidase enzymes that deconjugate testosterone-glucuronide, potentially increasing free testosterone levels in circulation.
• Some microbes can aromatize testosterone into estrogens, while others may influence testosterone production indirectly by affecting bile acid metabolism and enterohepatic circulation.

Factors Influencing Testosterone Metabolism

• Diet plays an important role in this relationship, as fiber-rich foods promote beneficial bacteria that may support optimal testosterone metabolism, while high-fat diets might foster microbes that increase testosterone clearance, as suggested by 1.
• The composition of one's gut microbiome can significantly impact testosterone levels, with dysbiosis potentially leading to hormonal imbalances.
• Other factors such as age, sex, and pet ownership can also influence the gut microbiome and, subsequently, testosterone metabolism, as reported in 1.

Clinical Implications

• This microbial influence on testosterone metabolism helps explain why gut health can affect hormone-related conditions and why probiotics or dietary interventions targeting the microbiome might influence hormone levels.
• Understanding the complex interactions between the gut microbiome and testosterone metabolism can inform the development of novel therapeutic strategies for hormone-related disorders, as implied by the findings of 1 and 1.

From the FDA Drug Label

Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways The major active metabolites of testosterone are estradiol and DHT.

The microbiome is not mentioned in the context of testosterone metabolism in the provided drug label. Testosterone metabolism is described as occurring through two different pathways, with the major active metabolites being estradiol and DHT. However, the role of the microbiome in this process is not addressed. 2

From the Research

Microbiome Metabolism of Testosterone

• The gut microbiota plays a significant role in the metabolism of androgens, including testosterone, in the intestinal tract 3.
• Studies have shown that the gut microbiota is involved in the deglucuronidation of testosterone and dihydrotestosterone (DHT), resulting in high levels of free DHT in the colonic content of young and healthy mice and men 3.
• The metabolism of testosterone by the microbiome can lead to the production of various metabolites, including glucuronidated and free forms of testosterone and DHT 3.
• The effects of the microbiome on testosterone metabolism can vary depending on factors such as the composition of the gut microbiota and the presence of specific bacterial species 4.

Mechanisms of Testosterone Metabolism

• Testosterone is metabolized by the gut microbiota through various mechanisms, including deglucuronidation and hydrolysis 3.
• The gut microbiota can also influence the expression of genes involved in testosterone metabolism, leading to changes in the levels of testosterone and its metabolites 4.
• The metabolism of testosterone by the microbiome can have significant effects on the host, including changes in hormone levels and metabolic pathways 5.

Implications for Human Health

• The metabolism of testosterone by the microbiome can have important implications for human health, including the development of metabolic disorders such as obesity and type 2 diabetes 5.
• Alterations in the gut microbiota have been linked to changes in testosterone levels and metabolic function, highlighting the importance of the microbiome in maintaining hormonal balance 4.
• Further research is needed to fully understand the mechanisms by which the microbiome metabolizes testosterone and the implications for human health 6.