title: Variation in Taxonomic Composition of the Fecal Microbiota in an Inbred Mouse Strain across Individuals and Time.
abstract: Genetics, diet, and other environmental exposures are thought to be major factors in the development and composition of the intestinal microbiota of animals. However, the relative contributions of these factors in adult animals, as well as variation with time in a variety of important settings, are still not fully understood. We studied a population of inbred, female mice fed the same diet and housed under the same conditions. We collected fecal samples from 46 individual mice over two weeks, sampling four of these mice for periods as long as 236 days for a total of 190 samples, and determined the phylogenetic composition of their microbial communities after analyzing 1,849,990 high-quality pyrosequencing reads of the 16S rRNA gene V3 region. Even under these controlled conditions, we found significant inter-individual variation in community composition, as well as variation within an individual over time, including increases in alpha diversity during the first 2 months of co-habitation. Some variation was explained by mouse membership in different cage and vendor shipment groups. The differences among individual mice from the same shipment group and cage were still significant. Overall, we found that 23% of the variation in intestinal microbiota composition was explained by changes within the fecal microbiota of a mouse over time, 12% was explained by persistent differences among individual mice, 14% by cage, and 18% by shipment group. Our findings suggest that the microbiota of controlled populations of inbred laboratory animals may not be as uniform as previously thought, that animal rearing and handling may account for some variation, and that as yet unidentified factors may explain additional components of variation in the composition of the microbiota within populations and individuals over time. These findings have implications for the design and interpretation of experiments involving laboratory animals.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Yana Emmy
authors.initials: YE
authors.lastname: Hoy
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Bik
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, United States of America.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Holmes
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Monack
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.|Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.|Howard Hughes Medical Institute, Stanford University, Stanford, California, United States of America.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Theriot
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.|Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.|Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Relman
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification*; D004032:Diet; D005243:Feces / Q000382:microbiology*; D005260:Female; D014644:Genetic Variation; D054892:Metagenome; D051379:Mice; D008815:Mice, Inbred Strains; D064307:Microbiota / Q000235:genetics*; D015233:Models, Statistical; D009711:Nucleotides / Q000235:genetics; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D009711:Nucleotides; D012336:RNA, Ribosomal, 16S