Effect of a Fructose-Rich Diet on Gut Microbiota and Immunomodulation: Potential Factors for Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the CNS that is linked with both genetic and environmental factors. A Western-style diet rich in fat and simple sugars is hypothesized as a potential factor contributing to the increased incidence of inflammatory autoimmune diseases, such as MS, in developed countries. Although the adverse effects of a high-fat diet in MS have been studied extensively, the effect of a fructose-rich diet (FRD) on MS etiology is unknown. We hypothesized that an FRD will alter the gut microbiome, influence immune populations, and negatively impact disease in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To test this, we fed C57BL/6 mice either an FRD or normal feed for 4 or 12 wk and analyzed the effect of an FRD on gut microbiota, immune populations, and EAE. An FRD significantly influenced the gut microbiota, with reduced abundance of beneficial bacteria and enrichment of potentially proinflammatory bacteria. We also observed immune modulation in the gut and periphery. Of particular interest was a population of Helios(−)RORγt(+)Foxp3(+)CD4(+) T cells that was enriched in the small intestine lamina propria of FRD-fed mice. However, despite gut microbiota and immune modulations, we observed only a subtle effect of an FRD on EAE severity. Overall, our data suggest that in C57Bl6/J mice, an FRD modulates the gut microbiota and immune system without significantly impacting myelin oligodendrocyte glycoprotein 35–55/CFA-induced EAE.