KLebsiella aerogenesa bacteria associated with poor clinical outcomes in hospitals, is more prevalent in the gut of premenopausal women with depression than in premenopausal women without depression, reports a study published today (March 17) in Cell metabolism. The authors identified a key enzyme in the bacteria’s genome that degrades estradiol, an ovarian hormone. Mice fed this bacterium or another designed to carry the enzyme showed lower estradiol levels and signs of depressive behaviors compared to control mice.
The fall in estradiol levels was related to female depression in men. After finding that levels of this steroid hormone were significantly lower in 91 postmenopausal women with depression than in 98 postmenopausal women without the mood disorder, a team from Renmin Hospital at Wuhan University, China , explored the influence of the gut microbiome on these differences. . By incubating faecal microbes from samples from either group with estradiol, the team found that those from patients with depression were significantly more effective at degrading estradiol than those from the group. not depressed. Additionally, fecal transplants of samples from the depressed group to mice induced depression-like behaviors in the animals.
In search of the species responsible for this degrading activity, the researchers cultured the faecal samples of the depressive group on a medium whose only carbon source was estradiol. Under these conditions, “a pale white colony with fuzzy edges and a smooth surface” developed, the researchers wrote in their paper, which they identified as a Gram-negative strain. K. airborne. By sequencing its genome, the team further discovered the presence of an estradiol-degrading enzyme, an enzyme that, worka team led by the same researchers had also reported degrading testosterone, inducing depressive-like behaviors in male mice.
Convert this enzyme into a Escherichia coli strain and administering it to female mice was sufficient to reduce estradiol levels in the blood, lower brain and hippocampus of the animals and induce depressive-like behaviors. By doing this final step, the team confirmed that this enzyme is “crucial” to what they are observing and that it is the activity of this enzyme that is “causing these effects”, says Brittany Needhammicrobiologist and neuroscientist at Indiana University School of Medicine, who was not involved in this work.
Finally, analyzes of the two groups of premenopausal women revealed that those with depression had a significantly higher abundance of K. airborne and its estradiol-degrading enzyme in faecal samples.
“They showed causation very well in mice,” meaning that feeding the mice bacteria that carried the enzyme changed the animals’ estradiol levels and behavior, Needham says. But this has not yet been demonstrated in humans, where so far there is only an association.
University of North Carolina-Chapel Hill School of Medicine David Rubinowho did not participate in this study, wrote in an email to The scientist that while animal studies like this “certainly provide some indication that [alterations of] gut bacteria can have some pretty striking phenotypic effects, for humans there’s more smoke than fire right now. Yet, he adds, “these data will encourage further studies on the [role of the] microbiome in affective disorders.