Effects of Food Matrix and Western Diet on Colorectal Cancer and Metabolism in C57BL/6 Mice

Abstract

Rodent studies that test the effects of bioactive dietary components on chronic disease generally use purified basal diets that were established using nutrient profiles optimized for growth and fertility such as the AIN93‐G diet which is not reflective of typical American macro and micronutrient intake. Previously, we used NHANES data to formulate the Total Western Diet (TWD), a rodent diet that emulates average American intake levels for macro and micronutrients using nutrient density. We have demonstrated that the TWD increases basal colorectal cancer (CRC) by ~2‐fold compared to the standard AIN93‐G diet in three different models. However, the TWD is comprised of purified ingredients and does not recapitulate the complex food matrix consumed by Americans. Using the latest version of the USDA Food Intakes Converted to Retail Commodities Database, we modified the TWD by using the most commonly consumed whole foods as dietary ingredients. The TWD2 has the same micro and macronutrient content as the previous TWD but contains 25 food ingredients including: sweeteners (sucrose and high fructose corn syrup); flours (wheat, potato, corn, rice and oat); meats (beef, poultry, pork, eggs and fish); dairy (lactose, whey and casein); fruits/vegetables (oranges, apples, bananas, grapes, strawberries, soy, snap beans, peanuts and cashews). To test whether food matrix affected CRC outcome, mice were fed either: AIN93‐G, TWD, TWD2 or TWD‐F (TWD matched for total fiber to TWD2). Mice were initiated with 10 mg/kg azoxymethane (AOM) and provided 1% dextran sodium sulfate (DSS) in their drinking water for 4 weeks to promote colonic inflammation and tumorigenesis. Necropsy and tumor assessment was performed after 15 weeks of treatment. A cohort of sham mice were fed the same diets but not injected with AOM or given DSS to determine effect of diets on metabolism and the gut microbiome. Mice fed the TWD, TWD‐F, and TWD2 did not differ in colon tumor multiplicity but all had significantly more tumors than mice fed the AIN93‐G diet (P < 0.01). Interestingly, mice fed the TWD2 diet consumed significantly more energy and gained more weight than all other treatments (P < 0.05). TWD2 fed mice also had significantly higher total fat mass, body fat percentage, and total visceral fat mass than AIN93‐G fed mice (P < 0.05) but not the purified TWD treatments. Lastly, TWD2 fed mice had significantly higher blood glucose concentrations than AIN93‐G fed mice, but not mice fed the purified TWD diets, at 90 and 120 minutes after oral glucose challenge (P < 0.05). Our data suggests that a diet with a complex food matrix, compared to purified diets with the same macro and micronutrient content, does not influence CRC but does increase energy consumption, adiposity, and glucose intolerance.Support or Funding InformationUtah Agricultural Experiment Station