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Article

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

1
Department of Animal, Dairy and Veterinary Sciences, 4815 Old Main Hill, Utah State University, Logan, UT 84322, USA
2
USTAR Applied Nutrition Research, 9815 Old Main Hill, Utah State University, Logan, UT 84322, USA
3
Department of Nutrition, Dietetics and Food Sciences, 8700 Old Main Hill, Utah State University, Logan, UT 84322, USA
4
Department of Food Science and Human Nutrition, the Institute for Integrative Toxicology, and the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
Received: 21 January 2020 / Revised: 12 February 2020 / Accepted: 17 February 2020 / Published: 20 February 2020
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 ApcMin/+ 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. View Full-Text
Keywords: Western diet; colitis; inflammation; colorectal cancer; calcium; vitamin D; transcript profiling Western diet; colitis; inflammation; colorectal cancer; calcium; vitamin D; transcript profiling
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    Doi: 10.26078/q4x4-6894
    Link: https://0-doi-org.brum.beds.ac.uk/10.26078/q4x4-6894
    Description: Supplemental data files are freely available at the Utah State University Digital Commons repository online at https://0-doi-org.brum.beds.ac.uk/10.26078/q4x4-6894, including File S1: Probe annotations.csv; File S2: Differential expression results.xlsx; File S3: Gene set analyses.xlsx; File S4: Pathway Z scores.xlsx; File S5: String-db networks and clusters.xlsx; File S6: Metascape ontology results.xlsx; File S7: Cell type scores.xlsx.
MDPI and ACS Style

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. https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020544

AMA Style

Benninghoff AD, Hintze KJ, Monsanto SP, Rodriguez DM, Hunter AH, Phatak S, Pestka JJ, Van Wettere AJ, Ward RE. Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice. Nutrients. 2020; 12(2):544. https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020544

Chicago/Turabian Style

Benninghoff, Abby D., Korry J. Hintze, Stephany P. Monsanto, Daphne M. Rodriguez, Ashli H. Hunter, Sumira Phatak, James J. Pestka, Arnaud J. Van Wettere, and Robert E. Ward 2020. "Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice" Nutrients 12, no. 2: 544. https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020544

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