Metabolites produced by microbes in the gut can ease inflammation in the central nervous system by limiting the damage done by microglia, an immune cell of the brain, an early study reports. Its scientists suggest this gut-brain axis may open new avenues to treatment.
“These findings provide a clear understanding of how the gut impacts central nervous system resident cells in the brain,” Francisco Quintana, PhD, of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH), and study lead author in a press release. “Now that we have an idea of the players involved, we can begin to go after them to develop new therapies.”
The study “Microglial control of astrocytes in response to microbial metabolites” was published in the journal Nature.
Two types central nervous system cells — microglia and astrocytes – are known to regulate inflammation and neurodegeneration in neurologic diseases, including multiple sclerosis (MS).
Microglia are the key immune cells of the central nervous system, patroling it for damaged cells and other materials in need of clearance. But microglia can impair and damage neighboring non-immune cells, the astrocytes, by releasing neurotoxic factors — such as the so-called VEGF-B — which were shown to worsen disease in a mouse model of MS.
BWH researchers have been investigating how the gut microbiome — the natural collection of microbes leaving within our gut — may influence the brain.
In this study, they found that byproducts released by gut-microbes as they break down dietary tryptophan — an amino acid (the building block of proteins) found in meats, dairy, fruits, and seeds — work to suppress the pro-inflammatory profile of microglia, halting their ability to promote via pathways pro-inflammatory activities in astrocytes.
Importantly, the team confirmed results working with brain tissue from MS patients. They saw that VEGF-B boosted a pro-inflammatory gene expression profile in primary human astrocytes.
“Our findings define a gut–brain axis by which metabolites of dietary Trp [tryptophan] controlled by the commensal flora act directly on CNS [central nervous system]-resident microglia and astrocytes to limit inflammation and neurodegeneration,” the researchers wrote.
“It is likely the mechanisms we’ve uncovered are relevant for other neurologic diseases in addition to multiple sclerosis,” Quintana said in the release. “These insights could guide us toward new therapies for MS and other diseases.”
The researchers plan to further investigate connections between the gut microbiome and neurologic diseases. They are developing small molecules and probiotics (live bacteria) to identify potential new factors important in the gut-brain axis that may lead to treatments.
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