Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
Institute of Pathology Überlingen, 88662 Überlingen, Germany.
Nutrients. 2019 Dec 23;12(1):45. doi: 10.3390/nu12010045.
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 ( < 0.05), changed microbiota composition and increased tumor promotion. On molecular level, the WD reduced proliferation ( < 0.05) and increased expression of the vitamin D catabolizing enzyme ( < 0.001). The switch to the AIN93G diet ameliorated this effect, reflected by longer colons, fewer ( < 0.05) and smaller ( < 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.
炎症性肠病会增加罹患结肠炎相关癌症的几率。我们假设西式饮食(WD)会加重氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的结肠炎相关肿瘤发生,并且即使在癌症发生后,切换到标准 AIN93G 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 AIN93G 饮食(AIN 组)。五周后,小鼠接受 12.5 mg/kg 的 AOM 腹腔注射,随后进行三个 DSS 循环。在一组小鼠中,在开始第一个 DSS 循环前一天(WD/AIN 组)将 WD 切换为 AIN93G。在整个实验期间给予 WD 会加重结肠炎症状,缩短结肠(<0.05),改变微生物群组成并增加肿瘤促进作用。在分子水平上,WD 降低了增殖(<0.05)并增加了维生素 D 代谢酶的表达(<0.001)。切换到 AIN93G 饮食改善了这种作用,表现为更长的结肠、更少(<0.05)和更小(<0.01)的异常结肠隐窝灶,与 AIN 组相当。我们的结果表明,即使在癌症发生后,切换到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。