Abstract
Accumulating evidence suggests that multiple sclerosis (MS) is an environmentally influenced disorder with contributions from life-time exposure to factors including Epstein-Barr virus infection or shifts in microbiome, diet and lifestyle. One suggested factor is a deficiency in propionic acid, a short-chain fatty acid produced by gut bacteria that may contribute to the disease pathology both in animal models and in human cases of MS. Propionate appears to exert beneficial effects on the immune, peripheral and central nervous systems of people with MS (pwMS), showing immunoregulatory, neuroprotective and neurogenerative effects. These functions are crucial, given that MS is characterized by immune-mediated damage of myelin in the central nervous system. Accordingly, propionate supplementation or a modulated increase in its levels through the microbiome and diet may help counteract the pro-inflammatory state in MS by directly regulating immune system and/or by decreasing permeability of gut barrier and blood-brain barrier. This could potentially improve outcomes when used with immune-modulating therapy. However, while its broad effects are promising, further large clinical trials are necessary to evaluate its efficacy and safety in pwMS and clarify its role as a complementary therapeutic strategy. This review provides a comprehensive analysis of the evidence, challenges and limitations concerning propionic acid supplementation in MS.