Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood

Significance Multiple sclerosis (MS) is classified as an autoimmune disease of the central nervous system (CNS). Alterations of gut microbiota (gut dysbiosis) are frequently observed in MS patients. It is still unknown how gut dysbiosis contributes to development of MS. We report here that gut dysbiosis, which we attribute to expansion of enteric pathogenic bacteria, triggers and/or exacerbates the spontaneous development of experimental autoimmune encephalomyelitis, an animal model of MS. This occurs during the period of young adulthood by reducing development of Foxp3 + Treg cells and expression of E3 ubiquitin ligase genes involved in protection from autoimmune diseases. This study suggests that gut dysbiosis may play a pathological role in the initiation and/or progression of MS during a defined age window.