Switching to a Healthy Diet Prevents the Detrimental Effects of Western Diet in a Colitis-Associated Colorectal Cancer Model
Switching to a Healthy Diet Prevents the Detrimental Effects of Western Diet in a Colitis-Associated Colorectal Cancer Model
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DOI：
10.3390/nu12010045
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发表时间：
2020-01-01
期刊：
影响因子：
5.9
通讯作者：
Kallay, Enikoe
中科院分区：
文献类型：
--
作者：
Groeschel, Charlotte;Prinz-Wohlgenannt, Maximilian;Kallay, Enikoe
炎症性肠病会增加患结肠炎相关癌症的几率。我们假设西式饮食（WD）抑制了氧化偶氮甲烷（AOM）/葡聚糖硫酸钠盐（DSS）诱导的结肠炎相关肿瘤发生，并且即使在癌症开始后，改用标准AIN 93 G饮食也会改善疾病症状。雌性BALB/c小鼠在整个实验期间接受WD（WD组）或标准AIN 93 G饮食（AIN组）。五周后，小鼠腹腔内接受12.5 mg/kg AOM，随后是三个DSS周期。在一组小鼠中，在开始第一个DSS周期的前一天将WD转换为AIN 93 G（WD/AIN组）。在整个实验期间喂食WD加重了结肠炎症状，缩短了结肠（p < 0.05），改变了微生物群组成并增加了肿瘤促进。在分子水平上，WD降低增殖（p < 0.05）并增加维生素D分解代谢酶Cyp 24 a1的表达（p < 0.001）。转换为AIN 93 G饮食改善了这种效果，反映为与AIN组相当的更长的结肠、更少（p < 0.05）和更小（p < 0.01）的异常结肠隐窝病灶。我们的研究结果表明，即使在癌症发生后，转向健康饮食也能够逆转WD的有害影响，并且可能是减少结肠炎症状和预防肿瘤发生的有效预防策略。
Inflammatory bowel disease increases the odds of developing colitis-associated cancer. We hypothesized that Western-style diet (WD) aggravates azoxymethane (AOM)/dextran sulfate sodium salt (DSS)-induced colitis-associated tumorigenesis and that switching to the standard AIN93G diet will ameliorate disease symptoms even after cancer initiation. Female BALB/c mice received either WD (WD group) or standard AIN93G diet (AIN group) for the whole experimental period. After five weeks, the mice received 12.5 mg/kg AOM intraperitoneally, followed by three DSS cycles. In one group of mice, the WD was switched to AIN93G the day before starting the first DSS cycle (WD/AIN group). Feeding the WD during the whole experimental period aggravated colitis symptoms, shortened the colon (p < 0.05), changed microbiota composition and increased tumor promotion. On molecular level, the WD reduced proliferation (p < 0.05) and increased expression of the vitamin D catabolizing enzyme Cyp24a1 (p < 0.001). The switch to the AIN93G diet ameliorated this effect, reflected by longer colons, fewer (p < 0.05) and smaller (p < 0.01) aberrant colonic crypt foci, comparable with the AIN group. Our results show that switching to a healthy diet, even after cancer initiation is able to revert the deleterious effect of the WD and could be an effective preventive strategy to reduce colitis symptoms and prevent tumorigenesis.