Mediterranean Pattern Diet in Multiple Sclerosis: A Review Focusing on Immunometabolites

Multiple Sclerosis (MS), the most common demyelinating disease of the Central Nervous System (CNS), is characterized in its pathogenesis by an interplay of mechanisms pertaining to aberrant immune response, acute and chronic inflammation, glial housekeeping, and neuron survival, ultimately resulting in demyelination, synaptic dysfunction, and neuroaxonal loss. Experimental models as well as epidemiological observations support the hypothesis of a role of diet in the disease onset, activity, and progression. It has been suggested that Western-type diets might be detrimental, while on the other hand, certain dietary regimens, like Mediterranean, low-fat, ketogenic, or intermittent fasting, might lead to disease amelioration, possibly through differential regulatory effects upon inflammation, immunity, and regenerative processes of neurons and glia. Under this perspective, immunometabolites, small intermediates including among the others citrate, itaconate, lactate, glutamate, glutamine, alfa-ketoglutarate, 2-hydroxyglutarate, fumarate, ceramides, whose turn-over reflects metabolic reprogramming of immune cells, might be viewed as significant regulators of cellular responses against either local or systemic noxious stimuli, both in the periphery and in the CNS. The present narrative review aims at summarizing current experimental and clinical evidence regarding the role of immunometabolites in shaping MS pathology, to address whether they could be relevant either as disease markers or therapeutic targets, and whether they might be differentially influenced by dietary approaches, especially by Mediterranean Pattern Diets (MPD).