Effects of the Food Matrix and Western Diet on the Mouse Microbiome

Rodent studies that measure effects of dietary components on the microbiome generally use basal diets such as the AIN diet series which is formulated with purified ingredients and has nutrient profile that optimizes growth and fertility and poorly models human intakes. 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. 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 the Western dietary pattern and/or the food matrix affected the microbiome, mice were fed for 15 weeks either: AIN93‐G, TWD, TWD2 or TWD‐F (TWD matched for total fiber to TWD2). Bacterial DNA from fecal samples harvested at sacrifice was extracted and microbiome composition was determined by 16s sequencing. Bacteriodetes was the majority phylum in mice fed the whole food TWD2 while Firmicutes was the majority phylum in all other treatments formulated with purified ingredients. Other notable phylum level differences included a significant increase in Proteobacteria ( P < 0.05) in TWD2 fed mice compared to the other treatments and increased Tenericutes in AIN93‐G fed mice compared to the other treatments ( P < 0.05). TWD2 fed mice had a significantly more diverse microbiome compared to all treatments except the TWDF (observed operational taxonomic units, P < 0.05). Lastly, beta diversity analysis revealed that TWD2 fed mice clustered apart from all other treatments as measured by principle coordinates analysis. Our data suggests that a diet with a complex food matrix, compared to purified diets induces profound changes in the microbiome even when macro and micronutrient contents are the same. Support or Funding Information Funding provided by the Utah Agricultural Experiment Station