Role of the Gut Microbiome as Determinant of Depression in MS Subjects
Abstract
The FY20 MSRP Focus Area of this application is Biology and measurement of multiple sclerosis (MS) symptoms. Depression is one of the most common symptoms in people with MS (pwMS) and when present it is a major cause of impaired quality of life, reduced productivity, and increased risk of developing other diseases or death. Depression in pwMS is a complex symptom. The exact cause of depression in pwMS is not well understood. Recent research identified a potential novel player involved in depression. This novel player is trillions of bacteria living in our own digestive system, collectively called the gut microbiome (or gut microbiota). Some of these bacteria secrete Gamma-Aminobutyric Acid (GABA), a key inhibitory molecule (more specifically a neurotransmitter) normally produced in the brain. GABA deficiency/imbalance has been linked to depression. This discovery suggests that the microbiome may affect depression via endogenous production of GABA from the gut. In addition, imbalance of the gut microbiome, such as overgrowth of pro-inflammatory bacteria and under-representation of anti-inflammatory bacteria, can contribute to systemic and brain inflammation, which is also a factor relevant in the development and persistence of depression. While the importance of the gut microbiome in depression has been increasingly recognized, it has not been studied in pwMS yet. Our preliminary results in a small cohort of pwMS showed encouraging data demonstrating an association of certain changes in the gut microbiome with depression. We found a decreased number of bacteria with GABA-producing potential and decreased number of anti-inflammatory bacteria in pwMS who had higher degree of depression. Interestingly, we found that specific dietary patterns were associated with a decrease of these beneficial gut bacteria. The main goal of this study is to confirm our finding in a larger cohort of pwMS with or without depression. We will also study the potential mechanism through which the gut microbiome can affect depression in pwMS. We will specifically focus on the role of the gut microbiome in modulating GABA production and inflammation. This project has clinical relevance and it has a translational potential for its nature. We believe that results from this research will benefit all pwMS by formally demonstrating a link between specific gut bacteria and depression in pwMS. Gaining this knowledge will allow us to evaluate strategies that could increase the abundance of protective bacteria and thus impact the symptom depression in pwMS. Dietary manipulation could be a possible therapeutic intervention to change gut microbiota composition and having effects on depression. The timeline for this project is 3 years. Once completed, we will have a good indication of the role of gut microbiota in depression in pwMS. Translation of these findings into the clinic will require the performance of larger randomized clinical trials to test microbiome-based interventions (e.g., dietary modification, probiotic treatment, fecal microbiota transplantation) in pwMS with depression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110937
Entities
People
- Laura Piccio
Organizations
- United States Army
- Washington University in St. Louis