Phenotype and Colonic Bacterial Relative Abundance Differ Between Mice from Two Different Facilities of the Same Vendor

Abstract

It is increasingly recognized that the phenotype of mice of the same strain used for biomedical research can vary considerably among different vendors. With the advent of next‐generation sequencing, the underlying basis of these phenotypic differences has been attributed to variation in gut bacterial community structure. Upon receiving mice from two different animal facilities (i.e., location) of the same vendor, we observed that the metabolic phenotype, e.g., insulin sensitivity, varied significantly. We hypothesized that the observed phenotypic differences were concomitant with changes in gut bacterial community structure. Our objectives were to i) measure glucose homeostasis and insulin sensitivity, ii) determine colonic bacterial relative abundance and diversity, and iii) analyze physiologic and bacterial data by facility and sex in adult mice. Three‐week‐old male and female outbred CD‐1 mice were received from two animal husbandry facilities (Cohort A and B; n=40/cohort/sex) of the same vendor. After one week of acclimation, mice were fed isoenergetic high‐fat (40% of total energy) diets for nine months. Feed intake and body weight were monitored, and, at nine months of age, glucose homeostasis and insulin sensitivity were evaluated via glucose tolerance test (GTT) and insulin tolerance test (ITT), respectively. Following the GTT and ITT, fecal samples were collected via 24‐hr metabolic cages. The V1‐3 region of bacterial 16S rRNA gene was amplified, and amplicons were sequenced via the Illumina Miseq (v.3) platform. Two‐way ANOVA with a post‐hoc Tukey test was utilized to detect differences in physiological parameters and colonic bacterial community structure between cohorts. Bacterial relative abundance was ranked prior to analysis. At nine months, feed intake was greater in Cohort A compared to Cohort B (P < 0.01), and total weight gain was greater in females of Cohort A compared to females of Cohort B (P < 0.01). In addition, males in Cohort B had greater fasting plasma insulin compared to males in Cohort A (P < 0.01) as well as greater insulin resistance as determined by HOMA‐IR (P < 0.001). At the phylum level, the relative abundance of Verrucomicrobia was greater in Cohort B compared to Cohort A (P < 0.01). Cohort B had a greater relative abundance of the genera Akkermansia and Clostridium compared to Cohort A (P < 0.05). No differences in colonic bacterial alpha diversity were found between cohorts. In conclusion, our results provide further support for recent evidence that colonic bacterial relative abundance can impact glucose homeostasis and insulin sensitivity. Moreover, these findings suggest that gut bacterial community structure is an important determinant in phenotypic variation of mice used for biomedical research, including strains procured from the same vendor.Support or Funding InformationArmin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA‐NIFA Hatch Fund (accession number: 1006628).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.