Diet high in simple sugars triggers TLR4 signaling pathway and promotes pro-inflammatory response via gut microbiota alteration

Diet is undoubtedly a strong modifier of microbiome and mucosal microenvironment in the gut. Components of western type diet have been associated with metabolic and immune diseases. Here, we compare the effects of high sugar (HSD) and high fiber diet consumption on gut mucosal barrier and immune response under steady state and during inflammation. We found that HSD increased intestinal permeability and induced pro-inflammatory response in healthy mice. In subsequent experiments, we observed that HSD worsened acute and chronic dextran sodium sulfate-induced colitis. In colon, HSD significantly promoted neutrophils infiltration and expression and production of pro-inflammatory cytokines. When colitis was induced in TLR4-/- mice the effect of HSD disappeared suggesting involvement of gut microbiome. Severe colitis was accompanied with significantly higher abundance of Escherichia coli and Candida genus in HSD mice. Anyway, when germ-free mice were colonized with microbiome of conventionally reared mice consuming different diets, colitis was equally severe in all groups suggesting that the presence of the diet was necessary for the effect. In conclusion, our observations suggest significant role of diet in preservation of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seem to be highly influenced by resident potentially pathogenic microbiota.