Gut Reaction

Diet and gut microbes can remotely influence brain inflammation

Immunofluorescence imaging of an active MS lesion in the brain. Image: Jorge Ivan Alvarez/School of Veterinary Medicine, Univ. of Pennsylvania

Immunofluorescence imaging of an active MS lesion in the brain. Image: Jorge Ivan Alvarez/School of Veterinary Medicine, Univ. of Pennsylvania

Bacteria living in the gut may remotely influence the activity of cells in the brain involved in controlling inflammation and neurodegeneration, new research led by Harvard Medical School investigators at Brigham and Women’s Hospital suggests.

Using preclinical models for multiple sclerosis and samples from MS patients, the team found evidence that changes in diet and gut flora may influence astrocytes in the brain, and, consequently, neurodegeneration, pointing to potential therapeutic targets. The team’s results were published in Nature Medicine.

“For the first time, we’ve been able to identify that food has some sort of remote control over central nervous system inflammation,” said corresponding author Francisco Quintana, HMS associate professor of neurology in the Ann Romney Center for Neurologic Diseases at Brigham and Women’s.

“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,” he said.

Previous investigations have suggested a connection between the gut microbiome and brain inflammation, but how the two are linked and how diet and microbial products influence this connection has remained largely unknown.

To explore this connection further, Quintana and colleagues performed genome-wide transcriptional analyses on astrocytes—star-shaped cells that reside in the brain and spinal cord—in a mouse model of MS, identifying a molecular pathway involved in inflammation.

They found that molecules derived from dietary tryptophan (an amino acid famously found in turkey and other foods) act on this pathway, and that when more of these molecules are present, astrocytes were able to limit brain inflammation. In blood samples from MS patients, the team found decreased levels of these tryptophan-derived molecules.

“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,” said Quintana.

The research team plans to investigate this pathway and the role of diet in future studies to determine whether the new findings can be translated into targets for therapeutic intervention and biomarkers for diagnosing and detecting the advancement of disease.

This work was supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, Mallinckrodt Pharmaceuticals, the German Research Foundation, the International Academy of Life Sciences, the Ministry of Science and Technology, Taiwan, and by a fellowship from CAPES, Brazil.

Adapted from a Brigham and Women’s news release.