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Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice

Falk Hildebrand12, Thi Loan Anh Nguyen1234, Brigitta Brinkman56, Roberto Garcia Yunta12, Benedicte Cauwe34, Peter Vandenabeele56, Adrian Liston34 and Jeroen Raes12*

Author affiliations

1 Department of Structural Biology, VIB, Pleinlaan 2, 1050 Brussels, Belgium

2 Department of Bioscience Engineering, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium

3 Autoimmune Genetics Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium

4 Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium

5 Department for Molecular Biomedical Research, VIB, Technologiepark Zwijnaarde 927, 9052 Ghent, Belgium

6 Department for Molecular Biomedical Research, GhentUniversity, Technologiepark Zwijnaarde 927, 9052 Ghent, Belgium

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Citation and License

Genome Biology 2013, 14:R4  doi:10.1186/gb-2013-14-1-r4

Published: 24 January 2013



Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing.


We find initial evidence for richness-driven, strain-independent murine enterotypes that show a striking resemblance to those in human, and which associate with calprotectin levels, a marker for intestinal inflammation. After enterotype stratification, we find that genetic, caging and inter-individual variation contribute on average 19%, 31.7% and 45.5%, respectively, to the variance in the murine gut microbiota composition. Genetic distance correlates positively to microbiota distance, so that genetically similar strains have more similar microbiota than genetically distant ones. Specific mouse strains are enriched for specific operational taxonomic units and taxonomic groups, while the 'cage effect' can occur across mouse strain boundaries and is mainly driven by Helicobacter infections.


The detection of enterotypes suggests a common ecological cause, possibly low-grade inflammation that might drive differences among gut microbiota composition in mammals. Furthermore, the observed environmental and genetic effects have important consequences for experimental design in mouse microbiome research.