title: Age and microenvironment outweigh genetic influence on the Zucker rat microbiome.
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?
authors.affiliation: Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Lees
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Swann
authors.affiliation: Cardiovascular and Gastro-Intestinal Disorders Innovative Medicines, AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, United Kingdom.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Poucher
authors.affiliation: Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Section of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, United Kingdom; Centre for Digestive and Gut Health, Imperial College London, London, United Kingdom.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Marchesi
mesh_terms: D000375:Aging; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D044822:Biodiversity; D004195:Disease Models, Animal; D004777:Environment; D005243:Feces / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D064307:Microbiota / Q000235:genetics*; D009765:Obesity / Q000382:microbiology*; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D017422:Sequence Analysis, DNA
chemical_list: D012336:RNA, Ribosomal, 16S