Age and microenvironment outweigh genetic influence on the Zucker rat microbiome

Lees, H., Swann, J., Poucher, S. M., Nicholson, J. K., Holmes, E., Wilson, I. D. and Marchesi, J. R. (2014) Age and microenvironment outweigh genetic influence on the Zucker rat microbiome. PLoS ONE, 9 (9). e100916. ISSN 1932-6203 doi: 10.1371/journal.pone.0100916

Abstract/Summary

Animal models are invaluable tools which allow us to investigate the microbiome-host dialogue. However, experimental design introduces biases in the data that we collect, also potentially leading to biased conclusions. With obesity at pandemic levels animal models of this disease have been developed; we investigated the role of experimental design on one such rodent model. We used 454 pyrosequencing to profile the faecal bacteria of obese (n = 6) and lean (homozygous n = 6; heterozygous n = 6) Zucker rats over a 10 week period, maintained in mixed-genotype cages, to further understand the relationships between the composition of the intestinal bacteria and age, obesity progression, genetic background and cage environment. Phylogenetic and taxon-based univariate and multivariate analyses (non-metric multidimensional scaling, principal component analysis) showed that age was the most significant source of variation in the composition of the faecal microbiota. Second to this, cage environment was found to clearly impact the composition of the faecal microbiota, with samples from animals from within the same cage showing high community structure concordance, but large differences seen between cages. Importantly, the genetically induced obese phenotype was not found to impact the faecal bacterial profiles. These findings demonstrate that the age and local environmental cage variables were driving the composition of the faecal bacteria and were more deterministically important than the host genotype. These findings have major implications for understanding the significance of functional metagenomic data in experimental studies and beg the question; what is being measured in animal experiments in which different strains are housed separately, nature or nurture?

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/38451
Identification Number/DOI	10.1371/journal.pone.0100916
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
Publisher	Public Library of Science
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