Lin Lihui, Li Ying, Zhou Gaoshi, Wang Ying, Li Li, Han Jing, Chen Minhu, He Yao, Zhang Shenghong
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Division of Gastroenterology, The Seventh Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
J Inflamm Res. 2022 Apr 21;15:2523-2537. doi: 10.2147/JIR.S361039. eCollection 2022.
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.
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.
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.
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.
西式饮食（WSD）与炎症性肠病（IBD）的患病率相关。然而，WSD对IBD发展的影响及其潜在机制仍不清楚。转录组学和代谢组学可能有助于识别与WSD相关的实验性IBD易感性的关键因素。然而，尚未进行此类研究。我们旨在使用这些高通量技术分析WSD对小鼠实验性结肠炎易感性的影响及其潜在机制。
从断奶开始，我们给实验小鼠喂食WSD和对照饮食。9周后，用2,4,6-三硝基苯磺酸处理小鼠以诱导结肠炎，对照组用50%乙醇处理（常用的IBD动物模型）。使用全基因组微阵列和液相色谱-串联质谱法鉴定有或没有疾病前WSD的实验性结肠炎的差异转录本和代谢物。
与对照饮食相比，WSD在实验性结肠炎中诱导了更严重的炎症。与对照饮食相比，我们发现在患有WSD的实验性结肠炎中有2540个基因上调和2737个基因下调。此外，41种结肠组织代谢物和56种血清代谢物的水平显示出显著差异。整合转录组学和代谢组学数据，我们发现了WSD促进实验性IBD易感性的主要共表达网络，包括生物转化酶、聚糖合成和代谢、类固醇激素代谢物。
疾病前WSD增加了实验性结肠炎的易感性。我们的结果可以为潜在机制提供重要证据，并有助于饮食建议以更好地管理IBD。
