Age and Microenvironment Outweigh Genetic Influence on the Zucker Rat Microbiome
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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?
Authors
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Comments
Related Content
Abstract
Introduction
Methods
Results
Discussion
Conclusions
Supporting Information
Author Contributions
References
Reader Comments (0)
Media Coverage (0)
Figures
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?
Date Issued
2014-09-18
Date Acceptance
2014-06-01
Citation
PLOS One, 2014, 9 (9)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
9
Issue
9
Copyright Statement
© 2014 Lees et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
HUMAN INTESTINAL MICROBIOTA
DISTAL GUT MICROBIOME
DIET-INDUCED OBESITY
ENERGY-BALANCE
MICE
ASSOCIATIONS
COMMUNITIES
RELEVANT
CAPACITY
ECOLOGY
Aging
Animals
Bacteria
Bacterial Typing Techniques
Base Sequence
Biodiversity
Disease Models, Animal
Environment
Feces
Intestines
Microbiota
Obesity
Phylogeny
RNA, Ribosomal, 16S
Rats
Rats, Zucker
Sequence Analysis, DNA
General Science & Technology
MD Multidisciplinary
Publication Status
Published
Article Number
e100916