Modelling western dietary habits in the mouse: easier said than done

Abstract

The recent debate on the relative importance of environmental vs. intrinsic factors in the onset of malignancy has raised major concerns that the general public might conclude that cancer prevention programmes are not worthwhile. In their original report (1), Tomasetti and Vogelstein concluded that a majority of cancers can be explained by the high number of stem cell divisions in tissues with a high cell turn-over, due to generation of random mutations and their accumulation each time DNA replicates. In a subsequent report (2), Wu and colleagues employed a different mathematical model and extended the data set to reach the opposing conclusion that spontaneous mutations occurring during stem cell division rarely reach the level necessary to underlie cancer development. In the majority of cases, exposure to environmental risk factors represents a fundamental requirement for the onset of malignant disease. Of note, in the mathematical approach of the former study (1), the intrinsic rate of stem cell division and the environmental risk factors were regarded as entirely independent variables whereas it is plausible to think that extrinsic factors do affect stem cell homeostasis.From this perspective, the study by Beyaz et al. The relevance of mouse studies for our understanding of the cellular and molecular mechanisms through which specific nutrients underlie colon cancer onset is largely dependent on our capacity to model western-style dietary habits in vivo with appropriate controls. From this perspective the diets employed in the Beyaz study raise a number of serious concerns.First, the control diet is a conventional "chow" (LabDiet, RMH3400) whereas the HFD is a purified product (Research Diets, D12492) produced by a different manufacturer and entirely different in nutrient levels when compared with the control diet. Of note, chow diets are typically used for 'maintenance' purposes because they provide complete and adequate nutrition at a relatively inexpensive price. However, they encompass plant-derived ingredients and are inappropriate for nutrition studies because of the high-dosage and variable levels of plant phytoestrogens. In chow-fed mice, serum phytoestrogens reach levels several orders of magnitude higher than endogenous estrogen, but are undetectable in animals fed with a purified diet (4,5). The substantial increase Commentary on NutritionModelling western dietary habits in the mouse: easier said than done

Effects of Rodent Diet Choice and Fiber Type on Data Interpretation of Gut Microbiome and Metabolic Disease Research

“…Current Protocols in Toxicology can play a role in data interpretation when both are used in the same study. The problem with using a GB diet as a control diet for a high fat purified ingredient diet has been discussed and recent surveys suggest this problem still can be found in many studies (Fodde, Schmitt, Schewe, & Augenlicht, 2017;Pellizzon & Ricci, 2018;Rendina-Ruedy & Smith, 2016;Warden & Fisler, 2008). In a recent survey of 69 publications including Cell, Nature, and Diabetes using search terms 'mouse high fat', it was found that only 18.8% of studies used a matched purified ingredient low fat control diet for the high fat diet while 40.6% used a GB diet as the low fat 'control' diet, with the remaining 40.6% of papers not providing sufficient data to determine what control diet was used (Pellizzon & Ricci, 2018).…”