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Exploring the gut-brain connection for insights into multiple sclerosis

BWH researchers find evidence that diet and gut microbes can remotely influence brain inflammation

Brigham and Women's Hospital

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IMAGE: Immunofluorescence imaging of human brain tissue generated from an active lesion from an individual with multiple sclerosis shows astrocytes (blue), the Aryl hydrocarbon receptor (red) and the phosphorylated Signal transducer... view more

Credit: Image courtesy of Jorge Ivan Alvarez, Assistant Professor at the Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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. Using pre-clinical models for multiple sclerosis (MS) 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 are published this week 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, PhD, an investigator in the Ann Romney Center for Neurologic Diseases at BWH. "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."

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 if the new findings can be translated into targets for therapeutic intervention and biomarkers for diagnosing and detecting the advancement of disease.

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

Paper cited: Rothhammer et al. "Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor" Nature Medicine DOI: 10.1038/nm.4106

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits and nearly 46,000 inpatient stays, is the largest birthing center in Massachusetts and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 3,000 researchers, including physician-investigators and renowned biomedical scientists and faculty supported by nearly $666 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

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