The Gut-Brain Connection and MS

At first glance, the idea that what happens in the gut can impact the brain might seem farfetched.  After all, the brain and the gut are far apart, and we know that the brain has a barrier that protects it from the rest of the body.  However, if we explore further, we see that the gut and the brain are actually quite connected, and this has important implications for MS and other disorders that affect the central nervous system.  

Gut Health and the Immune System

Particularly relevant for MS as an autoimmune condition, the environment in the gut has a heavy influence on the immune system.  With over 70% of the body’s immune system located in the gut, the gut has a unique opportunity to shape immune system development.  The gut is lined by epithelial cells that are charged with maintaining the integrity of the intestinal barrier, which is important for keeping everything in the gut in the right place so that the immune system does not get improperly activated.  Functions such as creating tight junctions between cells and maintaining a protective mucous layer are supported by the gut microbiota, the community of bacteria that live in the gut.  These bacteria work together with intestinal cells to provide signals to the immune system.  When new immune cells develop, the local environment in the gut serves as their training ground.  These interactions help determine whether immune cells will become more pro-inflammatory or more anti-inflammatory as they mature.  The cell’s identity will then determine its behavior when it goes out into the peripheral circulation.  In MS and other autoimmune diseases, we know there can be an imbalance in the immune system that favors inflammation.  Therefore, these interactions in the gut that shape immune cell behavior are critical.   

How the Gut Communicates With the Brain

Metabolites from the diet and molecules produced by intestinal cells and gut microbiota not only impact the local environment, but can also diffuse widely throughout the circulation.  For example, the intake of dietary fiber induces the production of short-chain fatty acids (SCFA’s) in the gut.  SCFA’s influence the local environment positively by helping with barrier integrity and promoting healthy immune development but also diffuse out into the bloodstream with far-reaching effects.  SCFA’s produced by the gut can impact the immune system distantly from the gut and also bind to receptors on organs like the liver and pancreas to promote healthy metabolism.  Importantly for MS, research has shown that SCFAs and other gut-derived metabolites can cross the blood brain barrier.  The gut also communicates with the brain through the vagus nerve, which connects them.  Gut-derived metabolites entering the brain from the circulation and signals transmitted by the vagus nerve can impact neurons, supporting cells like astrocytes, oligodendrocytes in myelin, and even immunologically relevant cells like microglia, all of which are known to be important in MS.   

The way the gut microbiota interact with the local immune system and the types of molecules that are produced in the gut are largely determined by the identities of the bacteria that live there.  Each person’s gut microbiota is as unique as a fingerprint. Research has demonstrated that there are differences in gut microbial composition in people who live with MS as compared to people who do not.  Whether altered gut microbial composition is causative in MS or a result of some other underlying process is not yet clear.  Treatment with disease-modifying therapies for MS is associated with gut microbial composition that more closely resembles that of people who do not live with MS.  

Supporting a Healthy Gut With Lifestyle Choices

There are certain factors influencing microbial composition that we cannot change, such as genetics, current age, and childhood illness exposures.  However, we know that lifestyle habits such as eating a healthy diet, getting regular exercise and physical activity, prioritizing sleep, and abstaining from smoking and alcohol help promote beneficial gut microbial composition and an overall healthy gut.  Antibiotics can be harmful to the gut microbiota and should be used only when truly necessary.    

Maintaining a healthy gut helps support immune balance, prevents and manages metabolic comorbidities, and promotes a healthy brain.  This is true for everyone, but even more important for people who live with MS.  Continuing research will help establish best practices for gut-related therapeutic strategies going forward.