Find in Library

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 (<i>p</i> &lt; 0.05), changed microbiota composition and increased tumor promotion. On molecular level, the WD reduced proliferation (<i>p</i> &lt; 0.05) and increased expression of the vitamin D catabolizing enzyme <i>Cyp24a1</i> (<i>p</i> &lt; 0.001). The switch to the AIN93G diet ameliorated this effect, reflected by longer colons, fewer (<i>p</i> &lt; 0.05) and smaller (<i>p</i> &lt; 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.