Multiple sclerosis (MS) is an autoimmune condition that affects the central nervous system (CNS) and leads to neuroinflammation. The chronic inflammatory cascades of the immune system damage the functions of the nerves and myelin tissue. The heterogeneity of MS symptoms depends on the anatomical location of the lesion within the CNS. The identification of the gut microbiota as a crucial modulator of neuroinflammation via the microbiota-gut-brain axis has been the subject of new studies. Butyrate, one of the well-known short-chain fatty acids (SCFAs) produced by gut bacteria through the fermentation of dietary fiber, exhibits notable immunomodulatory and neuroprotective properties. Along with the inhibition of histone deacetylases, the activation of G-protein-coupled receptors, and the facilitation of the transition of T helper 17 (Th17) cells to regulatory T (Treg) cells are some of the actions butyrate has. MS patients have fewer butyrate-producing bacteria and lower amounts of butyrate in their blood and intestines. It has been found that supplementing with butyrate in animal models can lead to the normalization of the blood-brain barrier (BBB) and the gut lining, the reduction of activated brain cells, the increase in myelin repair, and a decrease in T-cell responses to pathology. Butyrate also promotes regulatory B (Breg) cell function. The use of these therapies as an addition to traditional ones, such as dietary changes, the consumption of prebiotics or probiotics, and fecal microbiota transplantation, has shown favorable results in preliminary clinical studies. However, there are several challenges in translating these research-based preclinical evidences into clinical settings to treat MS. This review comprehensively summarizes the current evidence for butyrate-mediated mechanisms in MS and evaluates the potential of the gut microbiome as a therapeutic target.
