Scientists are increasingly recognizing that the gut microbiome plays an important role in overall health, including the brain. However, researchers are still working to determine exactly which specific bacteria are involved in the disease and how they affect the body.
In particular, some bacteria morganella morganiseveral studies have linked it to major depressive disorder. However, until recently, it was unclear whether this microbe contributes to depression, whether depression alters the microbiome, or whether another factor explains the association.
Researchers at Harvard Medical School have identified a biological mechanism that strengthens this claim. M. Morgany It can affect your brain health. Their findings provide a clearer explanation of how this bacterium affects depression.
Published in Journal of the American Chemical Societythis study points to molecules that cause inflammation and suggests potential new targets for the diagnosis or treatment of certain depressions. It also provides a framework for studying how other gut microbes shape human health and behavior.
“There have been theories linking the gut microbiome to depression, and this study takes another step toward truly understanding the molecular mechanisms behind this link,” said lead author John Clardy, Ph.D., Christopher T. Walsh Professor of Biochemistry and Molecular Pharmacology at the HMS Blavatnik Institute.
How environmental chemicals cause inflammation
Researchers have discovered that an environmental pollutant called diethanolamine (DEA) can replace sugar alcohols in molecules produced by the chemical. M. Morgany In the intestines.
This altered molecule behaves very differently than normal molecules. Instead of remaining harmless, it activates the immune system and prompts the release of inflammatory proteins known as cytokines, particularly interleukin-6 (IL-6).
This sequence of events offers potential explanations related to: M. Morgany To depression. Chronic inflammation is known to be involved in many diseases and has also been linked to major depressive disorder.
Previous research supports this relationship. Studies have linked IL-6 to depression and M. Morgany It is associated with inflammatory conditions such as type 2 diabetes and inflammatory bowel disease (IBD).
Further research will be needed to determine whether this altered molecule directly causes depression and to understand how many cases are affected by this process.
New possibilities for diagnosis and treatment
DEA is commonly found in industrial, agricultural, and consumer products.
“We knew that micropollutants could become incorporated into fat molecules in the body, but we didn’t know how that happened or what happened next,” Clardy says. “It was totally unexpected that DEA would be metabolized into immune signals.”
Researchers suggest that DEA could be used as a biomarker to help identify certain cases of major depressive disorder.
Their findings also lend weight to the idea that the immune system may be involved in depression, or at least some forms of it. This raises the possibility that treatments that target the immune response, such as immunomodulatory drugs, may be effective for some patients.
More broadly, this study shows how bacterial molecules can alter human immune function by uptake of pollutants. This insight could help scientists investigate how other gut bacteria affect immunity and various biological systems.
“Now that we know what we’re looking for, I think we can start looking at other bacteria to see if they have similar chemical reactions and start finding other examples of how metabolites affect us,” Clardy said.
Collaborative research advances microbiome science
This breakthrough was made possible by combining the expertise of two research groups. The Clardy Lab focuses on the chemistry of small molecules produced by bacteria, while the lab of Ramnik Xavier, HMS Kurt J. Isselbacher Professor of Medicine at Massachusetts General Hospital, specializes in understanding how the microbiome affects health at the molecular level.
These collaborations have increased our understanding of how gut bacteria interact with the immune system and influence disease. Their recent work includes:
- A single bacterium (A. muciniphila), the molecules it produces, the biological pathways it uses, and its effects on the body are linked (protecting against inflammation and increasing susceptibility to cancer immunotherapy).
- It shows that there are intestinal bacteria. R. Gunabas It produces immune-activating sugar chains, which may explain its association with Crohn’s disease and inflammatory bowel disease.
- Discovery of fatty molecules on the surface of Streptococcus bacteria Streptococcus pyogenes It may trigger the immune system to release inflammatory cytokines, which could help explain severe immune complications, possible links to autoimmune diseases such as lupus, and ways to improve cancer immunotherapy.
This fat molecule belongs to a group called cardiolipin and is known to stimulate the release of cytokines. In the new study, researchers found that when DEA is incorporated into the molecules produced, M. Morganybegins to act like cardiolipin and causes inflammation.
Authors, funding, and disclosures
Sunghee Bang and Yern-Hyerk Shin are co-lead authors. Additional authors are Sung-Moo Park, Lei Deng, R. Thomas Williamson, and Daniel B. Graham.
Co-author Xavier is a core member of the Broad Institute at the Massachusetts Institute of Technology and Harvard University, where he directs the Claman Cell Observatory and Immunology Program and co-directs the Infectious Disease and Microbiome Program.
This research was funded by the National Institutes of Health (grant R01AI172147) and the Leona M. and Harry B. Helmsley Charitable Trust (2023A004123). The authors also acknowledge the HMS Analytical Chemistry Core, the HMS Bio-molecular NMR Facility (formerly the East Quad NMR facility; NIH OD028526), and the Institute of Chemistry and Cell Biology (ICCB)-Longwood Screening Facility.
