Gut Bacteria Affects Myelin Content and Induces MS-Like Depression in Mice, Study Reports

Researchers at the Center of Excellence for Myelin Repair, a part of Mount Sinai, reported that gut bacteria produce compounds that were seen to affect the myelin content in mice and cause social avoidance behaviors. Study results indicated that targeting gut bacteria, or the gut metabolites, might help in treating neuropsychiatric disorders or complications, such as those caused by diseases like multiple sclerosis (MS).

The study, published in journal eLife, is titled “Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior.”

Previous studies from the same research team described a reduction of myelin and myelinated fibers in preclinical models of depression, postulating a biological explanation for the high rate of depression in patients with MS.

Now, the researchers identified bacteria-derived gut metabolites that can affect the content of myelin in the brains of mice and induce social avoidance behaviors, a depressive symptom.

In their experiments, the investigators transferred fecal bacteria from the gut of mice with depression to mice displaying no depressive symptoms. The microbiota transfer induced social avoidance behaviors, and altered the expression of myelin-related genes and myelin content in the brains of the recipient mice.

“Our findings will help in the understanding of microbiota in modulating multiple sclerosis,” Patrizia Casaccia, MD, PhD, professor of Neuroscience, Genetics and Genomics, and Neurology, and chief of the Center of Excellence for Myelin Repair, Icahn School of Medicine at Mount Sinai, said in a recent news release. “The study provides a proof of principle that gut metabolites have the ability to affect myelin content irrespective of the genetic makeup of mice. We are hopeful these metabolites can be targeted for potential future therapies.”

To explain the mechanism of gut-brain communication, the investigators identified communities of bacteria linked with increased levels of cresol, an organic compound capable of passing the blood-brain barrier.

When the precursors of cells that form myelin were exposed to cresol, they lost their capacity to produce myelin, indicating that a gut-derived metabolite had an impact in the formation of myelin in the brain.

More studies are necessary to translate the results from this study into humans, and to identify bacterial communities with the potential to encourage the production of myelin.

MS is a demyelinating disease in which the insulating covers (myelin) of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental and, in a number of patients, psychiatric problems.