Premenopause and depression: towards a new management pathway?

We are not all equal in the face of depression: women are twice as affected as men, probably due to hormonal differences. It has been shown in mice that the decrease in estradiol levels leads to a depressive syndrome. Estradiol is excreted into the digestive system via bile and partially reabsorbed. However, previous studies have shown that the passage of steroid hormones in contact with our digestive microbiota could affect their serum level. To find out more about the mechanisms involved, a Chinese team monitored 91 depressed women in their thirties and 98 other women without depression.

The role of microbiota

The results showed that estradiol levels were significantly lower (54 pg/mL vs 95 pg/mL) in depressed women. And their microbiota could be responsible for this: in vitro, after 2 hours, the microbiota of 5 depressed women was capable of degrading 77.8% of the 100 mg/L of estradiol added, compared to only 19.3% for the microbiota of 5 women without depression. Further, transplanting this “depressive microbiota” into mice was enough to decrease the rodents’ serum estradiol levels and morale.

Focus on Klebsiella aerogenes

The cause of this degradation is believed to be the bacterium Klebsiella aerogenes. A gavage experiment confirms this: mice consuming K. aerogenes exhibited reduced estradiol levels and depressive syndromes; the administration of an antibiotic to which the bacterium is sensitive was sufficient to suppress symptoms. Everything therefore seems to indicate that K. aerogenes degrades estradiol. Moreover, the bacterium can express the gene encoding the estradiol-degrading enzyme. And in depressed women, this bacterium and this enzyme are found to be more abundant. But K. aerogenes may not be the only gut bacterium capable of producing this enzyme. Other bacteria, such as Bacteroides thetaiotaomicron and Clostridia, could also be involved.

Targeting the bacteria

These preliminary findings could open up new treatment pathways to reduce depression in women: estrogen replacement therapy. The authors believe that the estradiol-degrading bacteria in the intestine, or even the enzymes expressed by these bacteria, could therefore constitute much better targets.