Abstract

The commensal gut microbiota has been implicated as a determinant in several human diseases and conditions. There is mounting evidence that the gut microbiota of laboratory mice (Mus musculus) similarly modulates the phenotype of mouse models used to study human disease and development. While differing model phenotypes have been reported using mice purchased from different vendors, the composition and uniformity of the fecal microbiota in mice of various genetic backgrounds from different vendors is unclear. Using culture-independent methods and robust statistical analysis, we demonstrate significant differences in the richness and diversity of fecal microbial populations in mice purchased from two large commercial vendors. Moreover, the abundance of many operational taxonomic units, often identified to the species level, as well as several higher taxa, differed in vendor- and strain-dependent manners. Such differences were evident in the fecal microbiota of weanling mice and persisted throughout the study, to twenty-four weeks of age. These data provide the first in-depth analysis of the developmental trajectory of the fecal microbiota in mice from different vendors, and a starting point from which researchers may be able to refine animal models affected by differences in the gut microbiota and thus possibly reduce the number of animals required to perform studies with sufficient statistical power.

Highlights

  • The commensal gut microbiota comprises hundreds of distinct microbial species which outnumber host somatic cells by an order of magnitude

  • Summary of 16S rDNA amplicons sequenced using the Illumina MiSeq platform and a set of 96 bar-coded primers, and the results of testing for strainand vendor-dependent interactions and main effects of strain and vendor on the relative abundance of consistently detected operational taxonomic units (OTUs) in the feces of 3.5, 7.5, 10.5, and 24 week old A/J, BALB/c, and C57BL/6 mice purchased from Harlan Laboratories and The Jackson Laboratory. *Significant interactions defined as an adjusted p value 0.05

  • These data suggest that the gut microbiota of laboratory mice assumes a strain-dependent structure within a larger vendor-specific range of possible compositions and that genetic background may slowly influence the composition of the fecal microbiota (FM) over time, the latter is not shown definitively

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Summary

Introduction

The commensal gut microbiota comprises hundreds of distinct microbial species which outnumber host somatic cells by an order of magnitude. Fecal Microbiota of Inbred Mice from Different Vendors development of culture-independent molecular techniques such as next-generation sequencing (NGS) [1]. Using these methodologies, associations have been made between a broad range of diseases and conditions and the human fecal microbiota (FM) [2]. Animal models, in which genetics and the external environment can be controlled and the FM can be manipulated as an independent variable, are needed to demonstrate causative relationships between the FM and associated diseases and conditions. An essential corollary to this line of inquiry is the uniformity of intestinal microbial populations in the animals used to model human disease, and whether any inherent differences impact those models. Considering recent calls for measures to enhance the reproducibility of preclinical biomedical research [4, 5], variability in the FM of research animals represents a potential confounding factor and necessary consideration for users of animal models

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