Depression in women: is bacteria to blame?

Nature is such that women, despite having no specific hormonal issues, are subject to an endless cycle of hormonal ups and downs from puberty to menopause. 
And that can lead to some drastic mood changes. One of the hormones involved is estradiol, which increases during the first half of the cycle and decreases in the second half. That explains why sex drive peaks during ovulation (when the hormone is at its peak) and morale tends to be rock solid during pregnancy (record levels). Conversely, women may feel blue during the second half of their cycle. But that’s not all. In premenopausal women suffering from depression, estradiol levels in the blood have been found to be almost half those of women of the same age with a sunny outlook. And the painstaking work of a Chinese team seems to have resulted in the naming of a culprit responsible for these depressive disorders: the gut microbiota Klebsiella aerogenes.

When microbiota degrades our hormones

Bear in mind that, in healthy individuals, estradiol is a hormone secreted in our digestive system via bile, which we then reabsorb. However, when it travels through the gut, the hormone comes into contact with our local microbiota. Some bacteria, especially K. aerogenes, are thought to have the ability to produce a molecule, called 3b-hydroxysteroid dehydrogenase (3b-HSD), an enzyme which chemically cuts estradiol and degrades it.

The 91 premenopausal women in their 30s with depression who agreed to take part in the trial were found to have a higher prevalence of both the bacteria and enzyme in their gut flora, compared to 98 women of the same age without depression. And if we mix their gut microbiota with estradiol in vitro (sidenote: In vitro Refers to an experiment performed in a test tube, outside a living organism. )  the microbiota degraded ¾ of the hormone in just two hours… while microbiota from women without depression destroyed four times less. Lastly, gavaging mice with microbiota from premenopausal women with depression, or simply K. aerogenes bacteria, was sufficient to cause depression-like behaviors in rodents.

Getting to the root of the problem

This work, which highlights the involvement of microbiota in depression in premenopausal women and how it operates, could have implications for the treatment provided to women with depression and their health. They are currently prescribed hormone replacement therapy, which comes down to increasing their estrogen levels. However, the cause of these health problems, i.e., bacteria found in the gut microbiota which are responsible for degrading the hormone, are not addressed. That’s why there is a risk of relapse when treatment is withdrawn. The authors believe that we need to get to the root of the problem, by directly targeting the bacteria that degrade estradiol in the gut, or even the enzymes expressed by those bacteria.