It has long been known that there is a link between our hormones, gut microbiome and mental health. Understanding the most relevant connections within our body, however, is not so simple. New research has discovered a single enzyme that links all three of these aspects, and its presence could be responsible for depression in women (and not only) of reproductive age.
Goodmorning sadness
There, medical researcher from Wuhan University, and his colleagues compared the blood serum of 91 depressed and 98 non-depressed women between the ages of 18 and 45. Incredibly, the depressed ones had almost half the serum estradiol levels, the main form of estrogen that our bodies use during the childbearing years. The research was published in Cell Metabolism (and I link it here)
Estradiol has been linked to depression in people with fertile female hormones for more than a century. And in fact, notoriously, its natural decline during menopause (and after pregnancy) is associated with negative changes in mood.
By investigating the dynamics of estradiol in the gut, the researchers found that a single organism in the gut microbiome is responsible for the decline in estradiol in the digestive system. It is a bacterial strain called Klebsiella aerogenes TS2020.
The “killer” of estradiol hides in the intestinal microbiome
Genetic analysis showed that Klebsiella aerogenes converts estradiol to estrone with an enzyme called 3β-HSD (3β-hydroxysteroid dehydrogenase). By injecting the gene for this enzyme into E. coli and infecting mice with these bacteria, scientists observed a drop in estradiol and the onset of depression in the mice.
The fact that giving estrone to control mice did not increase depressive-like behavior rules out excess estrone as a problem. Li and his colleagues also ruled out other molecules involved.
Mice affected with 3β-HSD also had lower levels of estradiol in the hippocampus brain region, which is known to be involved in depression. All this data suggests that the enzyme is the cause of brain problems linked to depression.
It should be emphasized that the link between the gut microbiome and depression is independent of gender: in a previous study, the same researchers had also identified increased levels of 3β-HSD in depressed male patients.
New therapeutic perspectives
Although estrogen replacement therapy has been considered as a possible treatment for depression in women, if the discovered mechanism is correct, the 3β-HSD-producing bacteria could cause relapses.
According to Li and his team, it would be more appropriate to target estradiol-degrading bacteria in the gut microbiome, and especially the enzymes expressed by these bacteria.
The discovery could be truly remarkable: over 280 million people worldwide suffer from depression. Create more effective therapies by understanding the links between the brain, intestine and hormones is a fantastic prospect.
We have always thought that the gut was our second brain. Considering the fact that it produces 95% of serotonin, the happiness hormone, and is also the cause of depression, perhaps the second brain is the other one, the one we have in the skull.
