Multi-Omics Analysis of Western-style Diet Increased Susceptibility to Experimental Colitis in Mice

Abstract

Background: Western-style diet (WSD) is associated with inflammatory bowel disease (IBD) prevalence. However, the impact of WSD on IBD development and its underlying mechanism remain unclear. Transcriptomics and metabolomics could be beneficial for identifying key factors in WSD-related experimental IBD susceptibility. However, no such study has been conducted yet. We aimed to analyze the implications of WSD for experimental colitis susceptibility in mice and its underlying mechanism using these high-throughput technologies. Methods: We fed experimental mice a WSD and a control diet from weaning. After 9 weeks, the mice were treated with 2,4,6 trinitrobenzene sulfonic acid to induce colitis, and the control group was treated with 50% ethanol (commonly used IBD animal model). Genome-wide microarray and liquid chromatography-tandem mass spectrometry were used to identify the differential transcripts and metabolites of experimental colitis with and without pre-illness WSD. Results: WSD induced more severe inflammation in experimental colitis than the control diet. We found 2540 up-regulated genes and 2737 down-regulated genes in experimental colitis with WSD compared with those for the control diet. In addition, levels of 41 colonic tissue metabolites and 56 serum metabolites showed significant differences. Integrating transcriptomic and metabolomic data, we found major co-expression networks through which WSD promoted experimental IBD susceptibility, including enzymes of biotransformation, glycan synthesis and metabolism, steroid hormone metabolites. Conclusion: Pre-illness WSD increased experimental colitis susceptibility. Our results could provide important evidences for the potential mechanisms and assist dietary recommendations to better manage IBD.