What is already known on this topic
Depression is one of the leading causes of disability worldwide, and low levels of the male sex hormone testosterone can lead to depressive symptoms in people. Yet, the causes of the lack of testosterone are unclear.
What this research adds
Researchers isolated the bacterium Mycobacterium neoaurum from people with depression and found that it could degrade testosterone. Administering M. neoaurum to rats lowered the rodents’ blood and brain levels of testosterone, inducing depressive-like behavior. Similar effects were observed when the rats were given Escherichia coli bacteria expressing an enzyme that degrades testosterone. The prevalence of this enzyme appears to be higher in people with depression.
The findings suggest that testosterone-degrading enzymes expressed by gut microbes are associated with depressive symptoms.
Depression can cause significant impairment in daily life and has become one of the leading causes of disability worldwide. New research has found a link between gut microbes and low levels of the male sex hormone testosterone, which can lead to depressive symptoms.
The findings, published in Cell Host & Microbe, suggest a role for gut microbes in certain types of depression by showing that testosterone-degrading enzymes expressed by gut microbes can be associated with depressive-like behavior.
Testosterone is a steroid hormone made in the testicles, adrenal glands, and adipose tissue. Low levels of testosterone can lead to depressive symptoms in people, and recent studies have shown that the gut microbiota can shift the ratio of active and inactive forms of some steroid hormones, thus influencing their levels. However, the causes of the lack of testosterone in some people remained unclear.
Researcher led by Zhongchun Liu, Gaohua Wang, Yan Li, and Tiangang Liu at Wuhan University hypothesized that some microbes in the gut of people with depression may degrade testosterone, resulting in lower blood levels of testosterone. So, they set out to investigate the link between the gut microbiota and testosterone deficiency.
First, the researchers analyzed testosterone levels in 77 people with depression and found that nearly 55% of them had lower-than-average levels of testosterone, compared to about 11% of 102 people without depression.
Transferring gut bacteria from people with depression to rats lowered testosterone levels and induced depressive-like symptoms, the researchers found.
Next, the team cultured the feces of people with depression in the presence of testosterone to isolate testosterone-degrading bacteria. They found that Mycobacterium neoaurum was the only microbe able to degrade testosterone.
To investigate whether M. neoaurum could cause depressive symptoms, the researchers gave it to rats by oral gavage. Rats that received M. neoaurum had lower blood and brain levels of testosterone than control rats. They also showed depressive-like behaviors. Treating rats with antibiotics normalized both the testosterone levels and behavior, the researchers found.
Similar effects were observed when rats were given Escherichia coli bacteria expressing 3β-hydroxysteroid dehydrogenase (3β-HSD), an enzyme that degrades testosterone. Giving the rats testosterone alleviated their depressive-like behaviors.
The researchers found that 3β-HSD is the key enzyme mediating testosterone degradation in M. neoaurum, and its prevalence appears to be higher in people with depression than in the general population.
“Our study revealed a mechanism potentially associating the degradation of testosterone by gut microbes harboring 3β-HSD with elevated depression risk,” the authors say. These findings could inform strategies for preventing testosterone deficiency and depressive disorders, they add.