Acclimation and Institutionalization of the Mouse Microbiota Following Transportation

Dan R Montonye,Aaron C Ericsson,Craig L Franklin,Cathleen Lutz,Susheel B Busi,Keegan Wardwell

doi:10.3389/fmicb.2018.01085

Abstract

Using animal models, the gut microbiota has been shown to play a critical role in the health and disease of many organ systems. Unfortunately, animal model studies often lack reproducibility when performed at different institutions. Previous studies in our laboratory have shown that the gut microbiota of mice can vary with a number of husbandry factors leading us to speculate that differing environments may alter gut microbiota, which in turn may influence animal model phenotypes. As an extension of these studies, we hypothesized that the shipping of mice from a mouse producer to an institution will result in changes in the type, relative abundance, and functional composition of the gut microbiota. Furthermore, we hypothesized that mice will develop a microbiota unique to the institution and facility in which they are housed. To test these hypotheses, mice of two strains (C57BL/6J and BALB/cJ), two age groups (4 week and 8 week old), and originating from two types of housing (research animal facility under conventional housing and production facilities under maximum barrier housing) were obtained from The Jackson Laboratory. Fecal samples were collected the day prior to shipping, immediately upon arrival, and then on days 2, 5, 7, and weeks 2, 4, and 9 post-arrival. Following the first post-arrival fecal collection, mice were separated into 2 groups and housed at different facilities at our institution while keeping their caging, diet, and husbandry practices the same. DNA was extracted from the collected fecal pellets and 16S rRNA amplicons were sequenced in order to characterize the type and relative abundance of gut bacteria. Principal component analysis (PCA) and permutational multivariate analysis of variance (PERMANOVA) demonstrated that both the shipping and the institution and facility in which mice were housed altered the gut microbiota. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) predicted differences in functional composition in the gut microbiota of mice based on time of acclimation.

Highlights

The transportation of laboratory mice from producers and animal facilities is a common occurrence in research
When analyzed by Principal component analysis (PCA), a clear separation of the preshipping and arrival time points was seen in the adult B6J CON mice (Figure 2B) with principal component (PC) 1 accounting for 38% of the variation
We show that the GM of mice is altered by the process of transportation from one institution to another

Summary

Introduction

The transportation of laboratory mice from producers and animal facilities is a common occurrence in research. From an animal welfare standpoint, it is important to recognize that these stress-like responses in animals do not necessarily indicate a pathologic change. Previous studies have shown that many alterations that occur in response to transportation normalize within 48–72 h following arrival, this can be highly variable (Ruiven et al, 1996; Conour et al, 2006; Obernier and Baldwin, 2006). Because of these findings, many institutions have adopted mandatory acclimation periods upon receiving transported mice that commonly range from 48 to 72 h. As addressed in the Guide for Humane Transportation of Research Animals (National Research Council, 2006), many factors such as age, strain, and length of shipment can extend the time required for normalization to weeks, and it is critical that investigators consider the effects of transportation in relation to their specific animal model

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