Diet is a strong modifier of microbiome and mucosal microenvironment in the gut. Recently, components of western-type diets have been associated with metabolic and immune diseases. Here, we studied how high-sugar diet (HSD) consumption influences gut mucosal barrier and immune response under steady state conditions and in a mouse model of acute colitis. We found that HSD significantly increased gut permeability, spleen weight, and neutrophil levels in spleens of healthy mice. Subsequent dextran sodium sulfate administration led to severe colitis. In colon, HSD significantly promoted neutrophil infiltration and increased the levels of IL-6, IL-1β, and TNF-α. Moreover, HSD-fed mice had significantly higher abundance of pathobionts, such as Escherichia coli and Candida, in fecal samples. Although germ-free mice colonized with microbiota of conventionally reared mice that consumed different diets had equally severe colitis, mice colonized with HSD microbiota showed markedly increased infiltration of neutrophils to the gut. The induction of colitis in Toll-like receptor 4 (TLR4)-deficient HSD-fed mice led to significantly milder colitis than in wild-type mice. In conclusion, our results suggested a significant role of HSD in disruption of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seemed to be highly influenced by resident potentially pathogenic microbiota or metabolites via the TLR4 signaling pathway.

BIOCEV Institute of Microbiology of the Czech Academy of Sciences Prumyslova 595 252 42 Vestec Czech Republic

Department of Analytical Chemistry Palacky University 17 Listopadu 1192 12 771 46 Olomouc Czech Republic

Department of Cell Biology Faculty of Science Charles University Vinicna 7 128 01 Prague Czech Republic

Department of Genetics and Microbiology Faculty of Science Charles University Vinicna 5 128 44 Prague Czech Republic

Faculty of Applied Sciences University of West Bohemia Univerzitni 8 301 00 Plzen Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

Laboratory of Fungal Genomics and Metabolism Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

Laboratory of Gnotobiology Institute of Microbiology of the Czech Academy of Sciences Doly 183 549 22 Novy Hradek Czech Republic

Laboratory of Molecular Structure Characterization Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

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