Figure 4.

Potential beneficial diet components and diet-gut microbiome interactions in the marmoset model of EAE

Specific components in whole milk, which is the base of the yogurt-based supplement (YBS), may have interacted with the immune system and the gut microbiome to decrease disease incidence and severity in the YBS-fed marmosets. (Left) Butyrophilin, the most abundant protein in the fat globule membrane in milk, has been shown to be immunomodulatory; it increases levels of anti-inflammatory IL-10 and decreases levels of pro-inflammatory IFN_Υ in EAE⁴⁴. (Center left) Members of the gut microbiome, such as Lactobacilli and Bifidobacterium spp., are capable of metabolizing dietary tryptophan into ligands of the aryl hydrocarbon receptor, such as indole-3-aldehyde and indole-3-lactic acid. These ligands influence glial cells, including astrocytes, and thereby reduce CNS inflammation and EAE disease scores^52,53. (Center right) N-glycans (carbohydrates that consist of several sugars linked to the nitrogen atom in the side chain of asparagine) present in milk serve as substrates for Bifidobacterium spp., which in turn produce SCFA as end products of carbohydrate fermentation. SCFAs have a direct impact on EAE by reducing Th1 cells and stimulating the proliferation of lamina propria-derived Treg^56,58. (Right) Proteolytic bacteria, such as Prevotella and Megasphaera spp., produce BCFA (iso-butyrate, valerate, and iso-valerate) as metabolic end products. Valproic acid is a valerate derivative that has anti-epileptic, neuro-protective, and anti-inflammatory effects and is capable of ameliorating symptoms in EAE and optic neuritis^64–66. EAE, experimental autoimmune encephalomyelitis; CNS, central nervous system; SCFAs, short-chain fatty acids; BCFAs, branched-chain fatty acids.