The etiology of Multiple Sclerosis (MS) is complex and not well understood. It is known that certain genetic factors, such as MHC, are strongly associated with the disease. Any environmental contributing factors are even less understood. However, there is compelling evidence that the gut microbiome may contribute to disease pathogenesis. Our lab has previously conducted fecal microbiome analysis on healthy vs. MS patients, and has shown that each group has a distinct microbiota. Certain bacterial genera, namely Prevotella, Adlercruitzia, and Parabacterodies, are more abundant in healthy individuals compared to patients with MS. These bacterial genera are known to metabolize phytoestrogens present in plant-based products, such as soybeans and flax seeds. We hypothesize that a healthy gut flora metabolizes certain foods, which leads to break down products (phytoestrogens) that induces and maintains the immune system to a regulatory state. A perturbation leading to decrease in these commensal bacteria might lead to disturbance of immune homeostasis and predisposition to develop autoimmune diseases, such as MS. We hypothesize that phytoestrogens metabolites (equol and enterolactone) induce regulatory immune cells through their interaction with intestinal epithelial cells, and/or immune cells at the intestinal mucosal sites. My project aims to decipher the role of phytoestrogen-metabolizing bacteria and their by-products on EAE. Specifically, we will determine the effects of these by-products on the local gut microenvironment. We will then determine the effects of the altered gut environment on CNS disease. To date, I have completed several preliminary experiments which suggest that phytoestrogen-metabolizing bacteria induce an anti-inflammatory environment in the gut.