Switching to a Healthy Diet Prevents the Detrimental Effects of Western Diet in a Colitis-Associated Colorectal Cancer Model.

Charlotte Gröschel,Michaela Lang,Denise Heiden,Maximilian Baumgartner,Abhishek Aggarwal,Martin Schepelmann,Rodrig Marculescu,Ildiko Mesteri,Sobha Karuthedom George,Samawansha Tennakoon,Maximilian Prinz-Wohlgenannt,Lena Trawnicek,Christoph Gasche,Enikö Kallay,Teresa Manhardt

doi:10.3390/nu12010045

Charlotte Gröschel, Michaela Lang + Show 13 more

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https://doi.org/10.3390/nu12010045

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Abstract

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.

Highlights

Incidence of inflammatory bowel diseases (IBD) is increasing continuously
We investigated whether the detrimental effect of a so-called “Western-style diet” (WD), high in animal fat but deficient in calcium, vitamin D, methyl donors, and fiber, on colitis-associated tumor formation can be prevented by switching the WD to the normal “healthy” AIN93G diet, containing soybean oil and adequate levels of micronutrients and fiber
After the first five weeks of feeding the test diets, i.e., at the time of AOM administration the body weight gain was similar in all three diet groups (Figure 2A), the energy content of the WD was roughly 15% higher

Summary

Introduction

Incidence of inflammatory bowel diseases (IBD) is increasing continuously. Standard therapies for ulcerative colitis and Crohns disease have limited efficacy [1]. Nutrients 2020, 12, 45 in industrialized regions of the world and the new onset in countries that are adopting a Western lifestyle suggest that a change in nutritional habits to a typical Western diet contribute to IBD [2,3]. IBD patients are at increased risk of developing inflammation-associated colorectal cancer (CAC) [4]. A recent meta-analysis reported that tumorigenesis in IBD patients occurs rather in the proximal colon and is associated with a worse prognosis compared with sporadic colorectal cancer (CRC) [5]. There is some evidence that proximal colon tumors develop more often in women [6]

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