Scientists report that gut flora can impact the behavior of the central nervous system.

Patients suffering from multiple sclerosis (MS) experience a wide range of neurological systems due to disruption of signals sent from nerves cells in the brain and spinal cord to other parts of the body. The disruption occurs because their own immune systems attack the myelin protein that covers the nerve cells. 

Scientists have been studying inflammation in the nervous system. They determined that microglia and astrocyte neural cells control inflammation and neurodegeneration by regulating pro-inflammatory and neurotoxic activities through communication with each other. The proteins TGF alpha and VEGF-B, which are produced by the microglia, control the processes. In a mouse model of MS, inflammation was halted with TGF alpha binds to receptors on the astrocytes, while inflammation was increased when VEGF-B binds to the astrocytes. 

The TGF alpha and VEG-B produced by the microalgia occurs in response to binding of the AHR receptor on the microglia by metabolites produced by gut bacteria as they break down tryptophan, a common dietary amino acid found in eggs, chocolate and dairy products. Binding on the metabolites blocked the production of inflammatory proteins and promoted the production of anti-inflammatory proteins, revealing that these small molecules manufactured in the gut travel throughout the body and directly affect nerve cells in the brain and spinal cord. 

Given these results, the researchers then looked at donated brain tissue from deceased MS patients. In areas where damage occurred due to MS, inflammation was caused by microglial cells and other immune cells that contained high amounts of TGF alpha and VEGF-B and expressed the AHR receptor for the tryptophan metabolites. When these cells were compared to non-damaged cells in the same brain tissues, it was found that the concentration of inflammation-blocking TGF alpha was much lower in the damaged cells.

Dr. Francisco Quintana of Brigham and Women’s Hospital notes that there is more work to do before these results can be applied to the development of treatments or recommendations on diets. The specific bacterial metabolites that affect the microglial inflammatory pathway have yet to be identified. Additional tests are also needed in humans to see how this knowledge translates to MS patients. "Multiple bacterial metabolites could be activating the pathways. We have currently focused on just one metabolite," he says. His group is, however, securing intellectual property agreements and developing potential probiotic supplements with pharmaceutical companies.

Dr. Bruce Bebo, Executive Vice President of Research at the National MS Society, which partly funded the study, is hopeful.  "It is complicated to dissect when this pathway is acting positively to suppress inflammation and promote repair or negatively, causing inflammation and blocking repair. This new research increases understanding of these pathways and is likely to lead to strategies and treatments which can slow down and even stop disability in MS. We hope that within the next few years, drugs can be found for trials and tested in patients.”