Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis

Abstract

Central to the understanding of the relationships between diet, gut microbiota, and vitamins D and A in multiple sclerosis is low-grade inflammation, which is involved in all chronic inflammatory diseases and is influenced by each of the above effectors. We show that food components have either proinflammatory or anti-inflammatory effects and influence both the human metabolism (the "metabolome") and the composition of gut microbiota. Hypercaloric, high-animal-fat Western diets favor anabolism and change gut microbiota composition towards dysbiosis. Subsequent intestinal inflammation leads to leakage of the gut barrier, disruption of the blood-brain barrier, and neuroinflammation. Conversely, a vegetarian diet, rich in fiber, is coherent with gut eubiosis and a healthy condition. Vitamin D levels, mainly insufficient in a persistent low-grade inflammatory status, can be restored to optimal values only by administration of high amounts of cholecalciferol. At its optimal values (>30 ng/ml), vitamin D requires vitamin A for the binding to the vitamin D receptor and exert its anti-inflammatory action. Both vitamins must be supplied to the subjects lacking vitamin D. We conclude that nutrients, including the nondigestible dietary fibers, have a leading role in tackling the low-grade inflammation associated with chronic inflammatory diseases. Their action is mediated by gut microbiota and any microbial change induced by diet modifies host-microbe interactions in a consequent way, to improve the disease or worsen it.

Keywords: Diet; Gut Microbiota; Multiple Sclerosis; Neuroinflammation; Vitamin D.

Fig. 1

A schematic representation of the effects of diet on gut microbiota. Gut is represented as the labyrinth at the Cathedral of Chartres, in France SCFA = short-chain fatty acid; AHR= ArylHydrocarbon receptor; Treg = regulatory T cell; Th = T helper; LPS = lipopolysaccharide; TNF = tumor necrosis factor; IL = interleukin; BBB = blood–brain barrier; VDR = vitamin D receptor

Fig. 2

The pathway from diet to neuroinflammation through gut dysbiosis Treg = regulatory T cell; Th = T helper; LPS = lipopolysaccharide; BBB = blood–brain barrier

Fig. 3

Cytochrome P450 (CYP) enzymes and the metabolism of vitamin D. Cholecalciferol is formed in the skin from 7-dehydrocolesterol after exposure to sunshine, then hydroxylated in the liver to 25-(OH)D3 (calcidiol) by the P450 enzymes CYP27A1 or CYP2R and subsequently activated in the kidney by CYP27B1 to 1α, 25-(OH)₂ D₃ (calcitriol), the active form of vitamin D. The latter is inactivated by CYP24A1 mainly to 1α,24,25-(OH)₃ D₃ (calcitroic acid). Therefore, active vitamin D levels depend on the relative rates of its synthesis via CYP27B1 and its modifications via CYP24A1

Fig. 4.

Role of active vitamin D and vitamin D receptor (VDR) in inflammation, through their binding to the retinoid X receptor (RXR), activated by retinoic acid (RA) VDR = vitamin D receptor; NF-κB = nuclear transcription factor kappa B; n-3 PUFA = omega-3 polyunsaturated fatty acids; RA = 9-cis-retinoic acid; SIRT-1/2 = sirtuins (deacetylating enzymes); NO = nitric oxide; ROS = reactive oxygen species; MMP = matrix metalloproteinase