Neurotoxic substances from gut bacteria found in patients with multiple sclerosis

The body’s microbiome is made up of bacteria and other microbes that form a symbiotic relationship enabling us to carry out many important metabolic processes. Recently, the species and numbers of microorganisms within the gut have been studied, some as potential biomarkers for various diseases.  As a result, three hazardous compounds generated by gut microbes have been detected in significant concentrations in individuals with multiple sclerosis (MS).

Toxic substances produced by these intestinal microbes may influence progression of the neurological illness, according to these groundbreaking results.

Various neurological diseases have been linked to bacteria in the gut, according to previous research. MS patients have higher levels of particular microorganisms in their digestive tracts compared to healthy people, however the way in which these organisms influence brain activity was still unknown – until now.

Gut bacteria / MS
A new study has identified gut-derived metabolites that appear to be neurotoxic and play a role in the progression of multiple sclerosis. (Credit: Nicoletta Barolini)

“Our findings suggest that MS patients’ gut bacteria produce and release large amounts p-cresol-sulfate, indoxyl-sulfate and N-phenylacetylglutamine into the bloodstream, and they eventually reach the cerebrospinal fluid,” says Hye-Jin Park, one of the lead authors on the study in a recent statement. Park is a research associate with the Neuroscience Initiative at the Advanced Science Research Center at the Graduate Center, CUNY (CUNY ASRC). “Once there, these toxic metabolites bathe the brain and spinal cord, and potentially play a role in the destruction of the myelin sheath that protect nerves,” adds Park.

Blood and cerebrospinal fluid were collected from MS patients at the Multiple Sclerosis Center of Northeastern New York. Pre- and post-treatment samples were collected from patients who were receiving the drug dimethyl fumarate (DMF), that has been shown to have a significant impact on the gut microbiota in those with MS. MS patients who did not take DMF had higher levels of the three distinct dangerous metabolites when compared to healthy people, according to the results. Additionally, they observed a decrease in the levels of toxic metabolites after DMF therapy.

“The presence of high levels of these toxic metabolites also correlates with biomarkers of neurodegeneration in MS patients, and with the ability to impair neuronal function of cultured cells in the laboratory,” says Achilles Ntranos, a lead author of the study and assistant professor of Neurology at the Icahn School of Medicine at Mount Sinai.

“This is an exciting and significant discovery,” adds Patrizia Casaccia, the study’s primary investigator and the founding director of the CUNY ASRC’s Neuroscience Initiative. “This work not only furthers our understanding of the role of gut-brain communication in neurodegenerative disease progression, but also provides a potential metabolic target for develop new MS Therapies.”

This study is published in Brain.


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