Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice
Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice
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DOI：
10.3390/nu12020544
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发表时间：
2020-02-01
期刊：
影响因子：
5.9
通讯作者：
Ward, Robert E.
中科院分区：
文献类型：
--
作者：
Benninghoff, Abby D.;Hintze, Korry J.;Ward, Robert E.
西方饮食的消费是结直肠癌的已知危险因素。我们的小组以前开发了西方饮食（TWD），用于模仿典型西方饮食的能量和营养谱的啮齿动物。在这项研究中，我们检验了以下假设：TWD的消费将增强结肠炎，延迟肠道损伤并促进结肠肿瘤发生。在多次实验中，使用甲氧基甲烷 +右旋钠硫酸钠或APC（Min/ +）与结肠炎相关的结直肠癌发生（CAC）（CAC）的APC（Min/ +）小鼠模型，我们确定喂食TWD的小鼠经历了更严重，更延长的结肠炎，并且与饲养标准的Ain93g饮食相比，最终增强了Collanced Colorig，而与之相比，它们的较重和更延长的结肠炎。此外，这种增加的肿瘤反应归因于TWD的微量营养素分数，而钙和维生素D的恢复为标准量，可以改善TWD的肿瘤促进作用。最后，暴露于TWD引起的大规模，与干扰素（IFN）反应，炎症，先天免疫，适应性免疫和抗原加工途径相关的结肠粘膜mRNA特征的动态变化。综上所述，这些观察结果表明，TWD的消耗显着增强了结肠炎，延迟肠道损伤的恢复以及结肠肿瘤的增加，可能是通过在结肠粘膜中的免疫相关基因表达的广泛变化而发生的。
Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis. In multiple experiments using the azoxymethane + dextran sodium sulfate or Apc(Min/+) mouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard AIN93G diet, ultimately leading to markedly enhanced colon tumorigenesis. Additionally, this increased tumor response was attributed to the micronutrient fraction of the TWD, and restoration of calcium and vitamin D to standard amounts ameliorated the tumor-promoting effects of TWD. Finally, exposure to the TWD elicited large scale, dynamic changes in mRNA signatures of colon mucosa associated with interferon (IFN) response, inflammation, innate immunity, adaptive immunity, and antigen processing pathways, among others. Taken together, these observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa.