Drawing a Line From the Gut Microbiome to Inflammation and Depression
upstart writes:
Study provides explanation for one bacterium's link to mental health:
It's become increasingly clear that the gut microbiome can affect human health, including mental health. Which bacterial species influence the development of disease and how they do so, however, is only just starting to be unraveled.
For instance, some studies have found compelling links between one species of gut bacteria, Morganella morganii, and major depressive disorder. But until now no one could tell whether this bacterium somehow helps drive the disorder, the disorder alters the microbiome, or something else is at play.
Harvard Medical School researchers have now pinpointed a biologic mechanism that strengthens the evidence that M. morganii influences brain health and provides a plausible explanation for how it does so.
The findings, published Jan. 16 in the Journal of the American Chemical Society, implicate an inflammation-stimulating molecule and offer a new target that could be useful for diagnosing or treating certain cases of the disorder. They also provide a roadmap for probing how other members of the gut microbiome influence human health and behavior.
"There is a story out there linking the gut microbiome with depression, and this study takes it one step further, toward a real understanding of the molecular mechanisms behind the link," said senior author Jon Clardy, the Christopher T. Walsh, PhD Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS.
The study reveals that an environmental contaminant known as diethanolamine, or DEA, sometimes takes the place of a sugar alcohol in a molecule that M. morganii makes in the gut.
This abnormal molecule then activates an immune response that the normal molecule does not, stimulating the release of inflammatory proteins called cytokines, particularly interleukin-6 (IL-6), the team found.
[...] DEA is used in industrial, agricultural, and consumer products.
"We knew that micropollutants can be incorporated into fatty molecules in the body, but we didn't know how this occurs or what happens next," Clardy said. "DEA's metabolism into an immune signal was completely unexpected."
The team proposes that DEA could be added to the growing list of biomarkers used to detect some cases of major depressive disorder.
The study also strengthens arguments that major depressive disorder, or a subset of cases, could be considered an autoinflammatory or autoimmune disease and be successfully treated with immune modulator drugs, Clardy said.
Journal Reference: DOI: 10.1021/jacs.4c15158
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