Why Is Multiple Sclerosis More Frequent in Women? Role of the Immune System and of Oral and Gut Microbiota

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system (CNS) with an autoimmune component affecting young adults in their third decade of life. The etiology is still undefined, but myelin damage is mainly due to an aberrant immune response of lymphocyte cells against myelin components. Therefore, inflammation, demyelination, and axonal degeneration represent the major pathologic hallmarks of the disease. There are many risk factors associated with MS, and probably the most relevant is gender-related. Women are up to four times more affected than men are. Although the female prevalence in MS is epidemiologically evident, the identification of key factors involved in this difference is under investigation. On the other side, if women are more affected, men show late onset and worse prognosis. This sexual dimorphism derives from many sources, including sex hormones, different genes on female sex chromosomes, and differences in bacterial species. Indeed, accumulating evidence proves a link among MS and gut microbiota where its dysbiosis could help the immune system to trigger neuroinflammation. In this context, oral biology alteration should be considered, too. This work is intended to explore current knowledge inside MS gender differences with a look towards oral–gut–brain axis involvement.