The Association of Tryptophan Metabolites, Gut Microbiota, and Chronic MS Symptoms
Abstract
Why do we need to do this study? After trauma, multiple sclerosis (MS) is the leading cause of disability in young adults. Aside from affecting the ability to walk, MS causes several chronic and disabling symptoms such as fatigue, depression, and difficulties with memory and slowing of processing speed. These chronic symptoms lower the quality of life for people with MS, negatively affect activities of daily living, and lead to unemployment and financial stress for people with MS and their families. The available treatments for these symptoms are not satisfactory and can have significant side-effects. There is no FDA-approved treatment for fatigue or cognitive dysfunction in MS. While major advances have been made in preventing new relapses and progression of physical disability in MS, we do not have a complete understanding of the causes underlying chronic cognitive and psychological symptoms of MS. Improved understanding of the mechanisms underlying these symptoms could lead to more targeted, efficacious, and safer treatments for these symptoms and ultimately improve quality of life for people with MS. Here, we propose to study changes in the metabolism of an amino acid called tryptophan and the gut bacteria that metabolize this amino acid and link these to the severity of these chronic and disabling MS symptoms. This proposal targets the MSRP Focus Area - Biology and Measurements of MS Symptoms. Tryptophan is an amino acid that is necessary for the production of several important chemicals in the brain that regulate sleep and mood in humans. We have shown that changes in the metabolism of this amino acid are associated with increased risk of development of MS, increased risk of relapse, and with changes in information processing speed. Other investigators have shown that bacteria living in human gut metabolize tryptophan and the derivates of tryptophan produced by the gut bacteria can affect inflammation in the brain. Based on these data, we hypothesize that changes in the gut bacteria alter tryptophan metabolism and these changes underlie fatigue, depression, and cognitive problems in patients with MS. What are the goals of the study? We aim to first identify whether the severity of MS symptoms including fatigue, depression, and cognitive dysfunction is linked to the levels of tryptophan derivatives in the blood. We will then link the abundance of tryptophan-metabolizing bacteria in the gut to levels of tryptophan derivatives in the blood. We will also link the abundance of tryptophan-metabolizing bacteria in the gut to the severity of MS symptoms. How will the study be conducted? We propose to determine the severity of fatigue, depression, and information processing speed in 50 people with MS and use state-of-the-art technology to measure tryptophan derivatives in the blood and study bacteria in the gut (identify bacteria capable of metabolizing tryptophan) in these people. We will then analyze if levels of the tryptophan derivatives are associated with severity of measures of fatigue, depression, and processing speed. We will also investigate if the abundance of gut bacteria that can metabolize tryptophan correlates with the level of tryptophan derivatives in the blood and if abundance of these bacteria is associated with symptom severity. We expect to find strong correlations between tryptophan derivatives in the blood, composition of gut bacteria, and severity of fatigue, depression, and cognitive dysfunction. What patient groups is this study likely to benefit? Fatigue, depression, and cognitive changes affect the majority of patients with MS. Patients with all subtypes of MS and all degrees of disability are affected by these symptoms. So, the results of this study will potentially be applicable to and benefit the majority of, if not all, patients with MS. What is the likely impact of the study? If tryptophan metabolism and gut bacteria are found to be associated with the severity
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010550
Entities
People
- Pavan Bhargava
Organizations
- Johns Hopkins University
- United States Army