Facility-dependent metabolic phenotype and gut bacterial composition in CD-1 mice from a single vendor: A brief report

Abstract

Utilization of murine models remains a valuable tool in biomedical research, yet, disease phenotype of mice across studies can vary considerably. With advances in next generation sequencing, it is increasingly recognized that inconsistencies in host phenotype can be attributed, at least in part, to differences in gut bacterial composition. Research with inbred murine strains demonstrates that housing conditions play a significant role in variations of gut bacterial composition, however, few studies have assessed whether observed variation influences host phenotype in response to an intervention. Our study initially sought to examine the effects of a long-term (9-months) dietary intervention (i.e., diets with distinct fatty acid compositions) on the metabolic health, in particular glucose homeostasis, of genetically-outbred male and female CD-1 mice. Yet, mice were shipped from two different husbandry facilities of the same commercial vendor (Cohort A and B, respectively), and we observed throughout the study that diet, sex, and aging differentially influenced the metabolic phenotype of mice depending on their husbandry facility of origin. Examination of the colonic bacteria of mice revealed distinct bacterial compositions, including 23 differentially abundant genera and an enhanced alpha diversity in mice of Cohort B compared to Cohort A. We also observed that a distinct metabolic phenotype was linked with these differentially abundant bacteria and indices of alpha diversity. Our findings support that metabolic phenotypic variation of mice of the same strain but shipped from different husbandry facilities may be influenced by their colonic bacterial community structure. Our work is an important precautionary note for future research of metabolic diseases via mouse models, particularly those that seek to examine factors such diet, sex, and aging.

Characteristics of gut microbiota in representative mice strains: Implications for biological research

“…The use of murine models in biomedical research is often an important and necessary step in developing better understanding of disease pathology, and there is a growing concern regarding the reproducibility of the results from murine‐based studies 57 . The mouse gut microbiota makes an important contribution to the explanation of these research results.…”

The microbiome and rodent models of immune mediated diseases

“…both bacteria and phages, of C57BL/6N mice could explain much of the phenotypic difference between mice from different vendors (Rasmussen et al 2019 ). Even differences in microbiota between different facilities from the same vendor can affect the metabolic phenotype of high-fat diet induced obese CD-1 mice (Unger et al 2020 ). The development of obesity and expression of the IFN-γ gene in the liver in these mice was reduced by phage transplantation in C57BL/6N mice (Rasmussen et al 2020 ).…”

Dietary fat quality impacts metabolic impairments of type 2 diabetes risk differently in male and female CD-1® mice

“…In addition, mice were subjected to intraperitoneal glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) every three months to evaluate glucose homeostasis and insulin sensitivity. These procedures have been previously described in detail in Unger et al (39) . Briefly, after a six-hour fast, GTTs (120 min in duration) began with an intraperitoneal injection of sterile 2 g/kg glucose (Sigma-Aldrich, St. Louis, MO, USA).…”