Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice

Authors

Abby D. Benninghoff, Utah State UniversityFollow
Korry J. Hintze, Utah State UniversityFollow
Stephany P. Monsanto, Utah State University
Daphne Michelle Rodriguez Jimenez, Utah State UniversityFollow
Ashli H. Hunter, Utah State UniversityFollow
Sumira Phatak, Utah State UniversityFollow
James J. Pestka, Michigan State University
Arnaud J. Van Wettere, Utah State UniversityFollow
Robert E. Ward, Utah State UniversityFollow

Document Type

Article

Journal/Book Title/Conference

Nutrients

Volume

12

Issue

2

Publisher

M D P I AG

Publication Date

2-20-2020

First Page

1

Last Page

35

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Related Content

Benninghoff, A. D. (2020). Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice. Utah State University. https://doi.org/10.26078/q4x4-6894

Abstract

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.

Recommended Citation

Benninghoff, A.D.; Hintze, K.J.; Monsanto, S.P.; Rodriguez, D.M.; Hunter, A.H.; Phatak, S.; Pestka, J.J.; Van Wettere, A.J.; Ward, R.E. Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice. Nutrients 2020, 12, 544.