Age and microenvironment outweigh genetic influence on the Zucker rat microbiome
Age and microenvironment outweigh genetic influence on the Zucker rat microbiome
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?
Aging, Animals, Bacteria/classification, Bacterial Typing Techniques, Base Sequence, Biodiversity, Disease Models, Animal, Environment, Feces/microbiology, Intestines/microbiology, Microbiota/genetics, Obesity/microbiology, Phylogeny, RNA, Ribosomal, 16S/genetics, Rats, Rats, Zucker, Sequence Analysis, DNA
1-11
Lees, Hannah
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Swann, Jonathan
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Poucher, Simon M.
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Nicholson, Jeremy K.
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Holmes, Elaine
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Wilson, Ian D.
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Marchesi, Julian R.
8945c0ab-7c63-44dd-a39c-3d084152959f
18 September 2014
Lees, Hannah
065ec499-13b2-4a01-bd6a-7e2102905c84
Swann, Jonathan
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Poucher, Simon M.
d0da9339-c2af-47d7-9c8c-88fd03e19753
Nicholson, Jeremy K.
72991774-7e08-4592-ae57-e7dcc2ec158e
Holmes, Elaine
d3b92a6b-1c3f-4758-b653-ba35afd3f57d
Wilson, Ian D.
d7da811b-6cc9-4166-82d0-e780c95122d2
Marchesi, Julian R.
8945c0ab-7c63-44dd-a39c-3d084152959f
Lees, Hannah, Swann, Jonathan, Poucher, Simon M., Nicholson, Jeremy K., Holmes, Elaine, Wilson, Ian D. and Marchesi, Julian R.
(2014)
Age and microenvironment outweigh genetic influence on the Zucker rat microbiome.
PLoS ONE, 9 (9), .
(doi:10.1371/journal.pone.0100916).
Abstract
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?
Other
journal.pone.0100916
- Version of Record
More information
Accepted/In Press date: 1 June 2014
Published date: 18 September 2014
Keywords:
Aging, Animals, Bacteria/classification, Bacterial Typing Techniques, Base Sequence, Biodiversity, Disease Models, Animal, Environment, Feces/microbiology, Intestines/microbiology, Microbiota/genetics, Obesity/microbiology, Phylogeny, RNA, Ribosomal, 16S/genetics, Rats, Rats, Zucker, Sequence Analysis, DNA
Identifiers
Local EPrints ID: 440709
URI: http://eprints.soton.ac.uk/id/eprint/440709
ISSN: 1932-6203
PURE UUID: 4792472f-c2f2-472a-bdf4-c1f9842f0521
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Date deposited: 13 May 2020 17:08
Last modified: 17 Mar 2024 04:00
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Contributors
Author:
Hannah Lees
Author:
Simon M. Poucher
Author:
Jeremy K. Nicholson
Author:
Elaine Holmes
Author:
Ian D. Wilson
Author:
Julian R. Marchesi
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