High Levels of Gut Bacterial Toxins Found in Spinal Fluid of MS Patients
People with multiple sclerosis (MS) have high levels of toxic compounds made by gut bacteria in the fluid around their brain and spinal cord, a study found.
“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” to develop new MS therapies, one of the scientists, Patrizia Casaccia, MD, PhD, of City University of New York (CUNY), said in a press release.
Findings were published in the study, “Bacterial neurotoxic metabolites in multiple sclerosis cerebrospinal fluid and plasma,” in Brain.
The digestive system is home to trillions of bacteria and other tiny organisms, collectively referred to as the gut microbiome. These organisms play important roles in health and disease that are only beginning to be understood.
An emerging body of research has indicated that the gut microbiome is altered in MS patients and may contribute to neurogeneration, but the exact components responsible for this gut-brain communication remain unidentified.
To find out, a team of scientists analyzed the cerebrospinal fluid (CSF) of people with relapsing-remitting MS, before or after treatment with dimethyl fumarate (sold as Tecfidera or generics). CSF is the liquid that surrounds the brain and spinal cord.
Results showed abnormally high levels of three molecules, made by bacteria in the gut, that are known to be toxic to nerve cells: p-cresol-sulfate, indoxyl-sulfate, and N-phenylacetylglutamine.
“Our findings suggest that MS patients’ gut bacteria produce and release large amounts [of] p-cresol-sulfate, indoxyl-sulfate and N-phenylacetylglutamine into the bloodstream, and they eventually reach the cerebrospinal fluid,” said Hye-Jin Park, a researcher at CUNY and study co-author.
Once these toxic compounds get into the CSF, they may contribute to the death of nerve cells and damage to the myelin sheath that occurs in MS. The compounds “may mediate gut-brain communication and induce neurotoxicity in multiple sclerosis,” the researchers wrote.
Additional analyses showed that levels of these toxic compounds tended to be higher in people with more profound brain damage on MRI scans. High levels of these compounds also were associated with higher levels of neurofilament light chain (NfL), a marker of nerve cell damage.
“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,” said Achilles Ntranos, MD, a lead author of the study and professor at the Icahn School of Medicine at Mount Sinai.
Treatment with dimethyl fumarate, which is known to drastically affect the gut microbiome in MS patients, markedly reduced levels of these toxic compounds.