Dietary habits and the composition of the gut flora can influence neuroinflammation and affect the outcome of neurodegenerative diseases such as multiple sclerosis (MS), according to a study published in the journal Nature Medicine and titled “Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammations via the aryl hydrocarbon receptor.”
Astrocytes, the brain immune cells, play an important role during central nervous system injury and disease, and are thought to participate in the pathogenesis of MS. Although the microbial flora and its products have been shown to control T-cell inflammation, through mechanisms that include the production of immunoregulatory metabolites from precursors provided through diet, little is known about the effects of diet and microbial products on the inflammatory response of immune cells in the brain.
Investigators at Brigham and Women’s Hospital (BWH) used preclinical models of MS and samples from MS patients to find that modifications in the diet and gut flora also influence astrocytes in the brain.
“For the first time, we’ve been able to identify that food has some sort of remote control over central nervous system inflammation,” said Francisco Quintana, PhD, the study’s senior author and an investigator in the Ann Romney Center for Neurologic Diseases at BWH, in a press release. “What we eat influences the ability of bacteria in our gut to produce small molecules, some of which are capable of traveling all the way to the brain. This opens up an area that’s largely been unknown until now: how the gut controls brain inflammation.”
Researchers performed a genome-wide transcriptional analysis on astrocytes in a mouse model of MS, and saw that the majority of the genes whose expression was modified were linked to interferon I (IFN-I), a signaling pathway involved in the reduction of inflammation.
The team showed that molecules derived from dietary tryptophan, an amino acid found in a variety of foods — such as chocolate, milk, nuts, meats, beans, cheese, and eggs — are metabolized by the gut flora, and act in combination with IFN-I in astrocytes to limit brain inflammation. Interestingly, tryptophan-derived metabolites were found to be decreased in the blood of MS patients.
“Deficits in the gut flora, deficits in the diet, or deficits in the ability to uptake these products from the gut flora or transport them from the gut — any of these may lead to deficits that contribute to disease progression,” Dr. Quintana said.
In the future, researchers plan to investigate whether these findings can be translated into biomarkers for diagnosing and detecting disease advancement, or into new targets for therapeutic approaches for neurological disorders.
