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Published on: December 15, 2011
Facility-dependent metabolic phenotype and gut bacterial composition in CD-1 mice from a single vendor: A brief
Allison L Unger1, Korin Eckstrom2, Thomas L Jetton3
1Department of Animal and Veterinary Sciences, The University of Vermont, Burlington, Vermont, United States of America.
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.
Insights
Murine model research is impacted by gut bacteria differences between facilities. These microbial variations significantly influence host metabolic phenotype, affecting study outcomes.
Area of Science:
- Microbiology
- Metabolic research
- Animal models
Background:
- Murine models are crucial for biomedical research, but phenotypic variability is a challenge.
- Gut bacterial composition is increasingly recognized as a factor influencing host phenotype inconsistencies.
- Housing conditions affect gut microbiota in inbred mice, but impact on intervention response is less understood.
Purpose of the Study:
- To investigate the impact of gut bacterial composition on metabolic phenotype variation in CD-1 mice from different husbandry facilities.
- To assess how diet, sex, and aging interact with facility-origin to influence metabolic health and glucose homeostasis.
- To determine if distinct gut microbial communities correlate with observed metabolic differences.
Main Methods:
- Long-term dietary intervention (9 months) with distinct fatty acid compositions in genetically-outbred male and female CD-1 mice.
- Comparison of mice from two different husbandry facilities (Cohort A and B).
- Analysis of colonic bacteria composition, including alpha diversity and differentially abundant genera, alongside metabolic phenotyping.
Main Results:
- Significant differences in colonic bacterial composition and enhanced alpha diversity were observed between Cohort A and B mice.
- Metabolic phenotypes, particularly glucose homeostasis, varied between cohorts and were linked to specific bacterial communities and diversity indices.
- Diet, sex, and aging differentially influenced metabolic phenotype based on the mice's facility of origin.
Conclusions:
- Gut bacterial community structure may explain metabolic phenotypic variation in mice of the same strain from different facilities.
- Husbandry facility origin is a critical factor to consider in mouse model studies, especially those involving diet, sex, and aging.
- Findings serve as a cautionary note for metabolic disease research using murine models, highlighting the importance of microbial standardization.
