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.

New research by investigators at Brigham and Women's Hospital (BWH) suggests that bacteria living in the gut may remotely influence the activity of cells in the brain that are involved in controlling inflammation and neurodegeneration.

To explore this connection further, \researchers performed genome-wide transcriptional analyses on astrocytes -- star-shaped cells that reside in the brain and spinal cord - in a mouse model of MS,  and identified type I interferons (IFN-Is) pathway involved in inflammation. IFN-I signaling in astrocytes reduces inflammation and experimental autoimmune encephalomyelitis (EAE) disease scores via the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) and the suppressor of cytokine signaling 2 (SOCS2). The anti-inflammatory effects of nasally administered interferon (IFN)-β are partly mediated by AHR.

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.  EAE scores were increased following ampicillin treatment during the recovery phase, and CNS inflammation was reduced in antibiotic-treated mice by supplementation with the tryptophan metabolites indole, indoxyl-3-sulfate, indole-3-propionic acid and indole-3-aldehyde, or the bacterial enzyme tryptophanase.

In blood samples from MS patients, the team found decreased levels of these tryptophan-derived molecules. The team's results are published in Nature Medicine.
 “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 the author.

These findings suggest that IFN-Is produced in the CNS function in combination with metabolites derived from dietary tryptophan by the gut flora to activate AHR signaling in astrocytes and suppress CNS inflammation.

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

http://www.brighamandwomens.org/about_bwh/publicaffairs/news/PressReleases/PressRelease.aspx?sub=0&PageID=2332