Previous studies have shown that good mood or depression is associated with estradiol levels.
They collected samples of gut microbiota from womenin premenopause with and without depression. Tests showed that within two hours, estradiol was degraded in the intestines of women with depression by 77.8% and only by 19.3% in subjects without depression. The results hint that even if both bodies of both groups of women were able to produce estradiol at healthy levels, something was still causing or accelerating its breakdown within the microbiome.
Researchers administered a "depressed" samplemicrobiome in mice. They found a 25% decrease in blood estradiol levels compared to the control group. Behavioral experiments showed depressive behavior in mice with lower estradiol levels. In summary, the gut microbiota of premenopausal women with depression decreased serum estradiol levels in mice and induced depressive behavior.
To understand the cause of the phenomenon, biologists isolatedpotential gut microbe that can degrade estradiol. They seeded laboratory dishes with estradiol as the sole carbon source and introduced the gut microbiota of the depressed group. The plate formed a pale white colony with fuzzy edges and a smooth surface. The scientists isolated one bacterium and identified it as Klebsiella aerogenes.
K.aerogenes was tested in isolation with estradiol. After incubation for five days, the researchers found that 61.8% of estradiol was converted to estrone. The researchers decided to retest the mice with the isolated microbe. This time, the researchers used three groups of mice: a control, one inoculated with K. aerogenes, and a third group also inoculated with the bacterium but given an additional antibiotic. The results confirmed that only K. aerogenes reduced estradiol levels in mice and caused depressive behavior. In addition, the antibiotic cefotaxime alleviated depressive behavior in mice.
Scientists have sequenced the entire genome of K.aerogenes and identified 3β-HSD, an enzyme produced by the microbe that can degrade estradiol into estrone. A new experiment in mice confirmed that the enzyme in question functions as expected. After mice were injected with E. coli with an inserted gene that produces 3β-HSD, they observed a drop in estradiol levels (by 45%) and depressive activity of the mice.
As a result, scientists realized that the prevalence of K.aerogenes and 3β-HSD are higher in the microbiomes of premenopausal women with depression compared to women without it. The researchers suggest that bacteria that degrade estradiol and 3β-HSD enzymes may be potential targets for treating depression in premenopausal women.
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