Megan M. Knuth, Carolina Vieira Campos, Kirsten Smith, Elizabeth K. Hutchins, Shantae Lewis, Mary York, Lyndon M. Coghill, Craig Franklin, Amanda J. MacFarlane, Aaron C. Ericsson, Terry Magnuson, Folami Ideraabdullah
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引用次数: 0
Abstract
Standard chow diets influence reproducibility in animal model experiments because chows have different nutrient compositions, which can independently influence phenotypes. However, there is little evidence of the role of timing in the extent of variability caused by chow exposure. Here we measured the impact of different diets (5V5M, 5V0G, 2920X and 5058) and timing of exposure (adult exposure (AE), lifetime exposure (LE) and developmental exposure (DE)) on growth and development, metabolic health indicators and gut bacterial microbiota profiles across genetically identical C57BL/6J mice. Diet drove differences in macro- and micronutrient intake for all exposure models. AE had no effect on phenotypic outcomes. However, LE mice exhibited significant sex-dependent diet effects on growth, body weight and body composition. LE effects were mostly absent in the DE model, where mice were exposed to chow differences only from conception to weaning. Both AE and LE models exhibited similar diet-driven beta diversity profiles for the gut bacterial microbiota, with 5058 diet driving the most distinct profile. However, compared with AE, LE effects on beta diversity were sex dependent, and LE mice exhibited nine times more differentially abundant bacterial genera, the majority of which were inversely affected by 2920X and 5058 diets. Our findings demonstrate that LE to different chow diets has the greatest impact on the reproducibility of several experimental measures commonly used in preclinical mouse model studies. Importantly, weaning mice from different diets onto the same diet for maturation may be an effective way to reduce unwanted phenotypic variability among experimental models.
期刊介绍:
LabAnimal is a Nature Research journal dedicated to in vivo science and technology that improves our basic understanding and use of model organisms of human health and disease. In addition to basic research, methods and technologies, LabAnimal also covers important news, business and regulatory matters that impact the development and application of model organisms for preclinical research.
LabAnimal's focus is on innovative in vivo methods, research and technology covering a wide range of model organisms. Our broad scope ensures that the work we publish reaches the widest possible audience. LabAnimal provides a rigorous and fair peer review of manuscripts, high standards for copyediting and production, and efficient publication.