Effects of Vendor and Genetic Background on the Composition of the Fecal Microbiota of Inbred Mice

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.

Exoelectrogenic capacity of host microbiota predicts lymphocyte recruitment to the gut

“…The GM of mice used in biomedical research is greatly simplified relative to that of feral mice (35), and the GM of mice purchased from the Jackson Laboratory exhibits a substantially lower microbial richness than that of HSD mice (9). Considering the limited resolution provided by 16S rRNA amplicon sequencing, there is the possibility that there are undefined taxa present within OTUs that annotated to higher taxonomic levels such as family or order involved in the differential current production.…”

Safety and risk assessment for the human superorganism

“…Because we viewed the healthiest humans as generally free of microbes, we designed safety evaluation and risk assessment models that unintentionally excluded or at least ignored a major part of us, the microbiome (Sleator 2010;Ericsson et al 2015;Dietert 2016a). The most comprehensive data from validated protocols, whether used for chemical, drug, physical agent, or microbial safety, were based on what we now know as a non-existent, biologically incorrect, incomplete form of humans: the human as a single species, purified form of mammal.…”

“…The most comprehensive data from validated protocols, whether used for chemical, drug, physical agent, or microbial safety, were based on what we now know as a non-existent, biologically incorrect, incomplete form of humans: the human as a single species, purified form of mammal. In failing to account for the effects of the human microbiome in modeling, we failed to analyze and include microbiome information from our test models, or failed to adequately control for what is now recognized as an important variation among microbiomes (Ericsson et al 2015).…”

Preclinical modeling of hematopoietic stem cell transplantation – advantages and limitations

“…Although inbred mice should share identical genetic backgrounds, the same inbred mouse strains from different vendors have been shown to exhibit different degrees of radiosensitivity and GVHD severity [8]. This may be due to several factors, including differences in feed and population, microbiomes, differing SPF environments, genetic drift, or a combination of these [9][10][11]. Therefore, application of the same transplantation model under identical conditioning regimens and treatments, but using mice from different vendors, may result in different degrees of engraftment and severity of GVHD.…”