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Cell Rep. 2019 May 7;27(6):1910-1919.e2. doi: 10.1016/j.celrep.2019.04.023.

Comparison of Co-housing and Littermate Methods for Microbiota Standardization in Mouse Models.

Author information

1
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
3
Ronin Institute, Montclair, NJ 07043, USA.
4
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
5
Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
6
Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, Ontario M5S 3B2, Canada.
7
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
8
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Electronic address: dana.philpott@utoronto.ca.

Abstract

The intestinal microbiota is a fundamental factor that broadly influences physiology. Thus, studies using transgenic animals should be designed to limit the confounding effects of microbiota variation between strains. Here, we report the impact on intestinal microbiota of co-housed versus F2-generation littermates, two commonly used techniques to standardize microbiota in animal models. Our results establish that while fecal microbiota is partially normalized by extended co-housing, mucosal communities associated with the proximal colon and terminal ileum remain stable and distinct. In contrast, strain inter-crossing to generate F2 littermates allows robust microbiota standardization in fecal, colon, and ileum sampling locations. Using reciprocal inter-crosses of P1 parents, we identify dissymmetry in F2 community structures caused by maternal transmission, in particular of the Verrucomicrobiaceae. Thus, F2 littermate animals from a unidirectional P1 cross should be used as a standard method to minimize the influence of the microbiota in genotype-phenotype studies.

KEYWORDS:

co-housing; intestinal; littermates; microbiota; microbiota standardization; mouse

PMID:
31067473
DOI:
10.1016/j.celrep.2019.04.023
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