Scientists have long suspected that the gut microbiome has opinions about your mental health, but proving which specific bacteria are responsible has been about as easy as herding cats - or, more accurately, microbes. Now, researchers at Harvard Medical School have identified a biological mechanism that suggests one particular bacterium, Morganella morganii, might be contributing to depression by turning an environmental contaminant into an inflammatory signal.
The study, published in the Journal of the American Chemical Society, points to diethanolamine (DEA), a chemical commonly found in industrial and consumer products. When DEA sneaks into a molecule produced by M. morganii, the molecule apparently forgets its usual harmless behavior and starts acting like a cardiolipin, a type of fatty molecule known to trigger immune responses. This activates the immune system, releasing inflammatory proteins called cytokines, particularly interleukin-6 (IL-6). Chronic inflammation has been linked to major depressive disorder, so the chain of events provides a plausible explanation for how a gut bug might mess with your brain.
“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 at HMS. The researchers suggest that DEA could potentially serve as a biomarker to identify certain cases of depression, and their findings add weight to the idea that some forms of the condition may involve the immune system, raising the possibility of treatment with immune-modulating drugs.
More broadly, the study demonstrates how a bacterial molecule can change human immune function by incorporating a contaminant. “Now that we know what we’re looking for, I think we can start surveying other bacteria to see whether they do similar chemistry and begin to find other examples of how metabolites can affect us,” said Clardy. The research was made possible by combining the Clardy Lab’s expertise in bacterial chemistry with the lab of Ramnik Xavier, the HMS Kurt J. Isselbacher Professor of Medicine at Massachusetts General Hospital, which specializes in microbiome health. Co-first authors Sunghee Bang and Yern-Hyerk Shin, along with additional authors, contributed to the work, which was funded by the National Institutes of Health and The Leona M. and Harry B. Helmsley Charitable Trust.