New research identifies a link between a specific gut bacterium and depression in women.

We’ve written about the gut and its microbiome and how they can influence the brain and mental health. We’ve also specifically examined some ways in which the microbiome can cause depression in men and women, and the sort of testing that can survey gut health and brain health, as well as the food sensitivities and allergies that can cause gut dysbiosis in the first place. Our previous articles can be found on our website. The microbiome is incredibly complex, and intense research is being focused on it to unwind those complexities and document how specific gut flora affects the microbiome and how in turn that links to other systems in the body. Even if every microbiotic interaction isn’t entirely in focus yet, a few things are clear: The microbiome can be heavily influenced by what we eat, whether that’s because we make the wrong food choices, or because of allergies and sensitivities; inflammation in the gut can cause inflammation in other parts of the body, and that inflammation can become chronic; there is a strong gut-brain connection, and that connection can cause gut dysbiosis to strongly influence the disposition of neurotransmitters.

A recent discovery about a specific gut bacterium and its influence outside of the microbiome makes a compelling case that the bacterium downregulates estradiol, and in turn can promote depression in pre-menopausal women. That bacterium is Klebsiella aerogenes, formerly known as Enterobacter aerogenes, before being reclassified after genetic analysis. This bacterium has been found to degrade estradiol and induce depressive-like behavior in mice in a recent study. Klebsiella bacteria are known to be associated with poor outcomes and even death in hospital settings and can be introduced iatrogenically. Writing about the study in the Scientist on March 17, 2023, Alejandra Manjarrez, PhD notes: 

“The authors identified a key enzyme in the bacterium’s genome that degrades the ovarian hormone estradiol. Mice fed this bacterium or a different one engineered to carry the enzyme had lower estradiol levels and evidence of depressive-like behaviors compared to control mice. Declining estradiol levels have been linked to female depression in humans.”

The study compared menopausal women with depression with those who did not have depression and discovered that estradiol levels were lower in those women who were depressed. They then collected fecal samples from the women and incubated them with estradiol. This resulted in the degradation of estradiol in the samples from the group of depressive women. In addition, fecal transplant from the degraded estradiol samples into mice caused depressive behavior in the mice.  In searching for the particular agent for this degradation, they cultured the degraded estradiol fecal samples and discovered that the resultant growth was the bacterium  Klebsiella aerogenes. A previous study found that this same bacterium degrades testosterone. 

“By sequencing its genome, the team further found the presence of an estradiol-degrading enzyme—an enzyme that, in earlier work, a team led by the same researchers had reported also degrades testosterone, inducing depressive-like behaviors in male mice.

Engineering this enzyme into an Escherichia coli strain and feeding it to female mice was sufficient to reduce the animals’ blood, lower brain, and hippocampus estradiol levels 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 Needham, a microbiologist and neuroscientist at Indiana University School of Medicine, who was not involved in this work Finally, analyses of both groups of premenopausal women revealed that those exhibiting depression had significantly higher abundances of K. aerogenes and its estradiol-degrading enzyme in fecal samples. (Scientist again)

This is excellent science and demonstrates a chain of cause and effect directly from Klebsiella aerogenes to depression, in this case in women. Given that the same effect was charted in men from the same bacterium, Klebsiella aerogenes seems to be a smoking gun for estradiol degradation. This is not to say that many other things can’t degrade estradiol, but if a patient has both low estradiol and gut dysbiosis, then Klebsiella aerogenes might be the culprit.

So how should you assess that? You could start by assessing estradiol levels, and since the same mechanisms seem to be in play for men, assess testosterone levels for male patients. The Female Functional Wellness Panel from Precision Point Diagnostics includes an analysis of estradiol as part of a comprehensive female wellness analysis. Our Male Functional Wellness Panel includes testosterone as part of a comprehensive male wellness analysis. Particularly for female or male patients who are depressed, it makes sense to order these profiles to check estradiol or testosterone levels since both have been linked to depression, as well as to have a functional assessment of general health.

What about measuring Klebsiella aerogenes specifically? This is difficult. There are very few tests for the specific species, and normally this wouldn’t be ordered unless a patient was very ill indeed, especially after a stay in the hospital. On the other hand, since Klebsiella aerogenes is detected as either Klebsiella pneumoniae/variicola or as Klebsiella oxytoca, and as these are the most common occurrences of Klebsiella, then it makes sense to screen for these most common variants in the average patient who exhibits both gut dysbiosis and low estradiol/testosterone rather than ordering rare and expensive testing for Klebsiella aerogenes specifically without there being a specific reason for it. If a patient tests positive for any  Klebsiella, and low estradiol or testosterone, then further testing may not be warranted to infer that Klebsiella aerogenes is the cause. Precision Point Diagnostics offers the GI360™ Profile stool test to evaluate a wide range of GI assessments including the Klebsiella variants  Klebsiella pneumoniae/variicola and Klebsiella oxytoca. If further testing seems desired to zero in on the cause, then that can always be pursued after initial testing. It seems likely that testing for the most common Klebsiella species will also include Klebsiella aerogenes,  which should have clinical significance for those with depression- especially those who present with gut dysbiosis.