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Variation in Taxonomic Composition of the Fecal Microbiota in an Inbred Mouse Strain across Individuals and Time.

Hoy YE, Bik EM, Lawley TD, Holmes SP, Monack DM, Theriot JA, Relman DA - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.

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.

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Comparison of variation within and between mice.(a) The average pairwise weighted UniFrac distances between technical replicates (includes all replicates—biological, extraction, sequencing run, and barcode), within 43 individual mice over less than two weeks (14 days), within four individual mice over 15–31 days, within four individual mice over 32–250 days, and among all different healthy mice. Bar height indicates mean; thin lines at the top indicate the standard error. All categories were significantly different from the technical replicates. ***, p<0.001. NS, non-significant. (b) Average pairwise weighted UniFrac distances between samples collected from the same mice at different times, plotted against time interval between sampling, for up to 14 days. The line represents the linear regression slope. (c) Same as (b) except that time intervals are as long as 236 days.
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pone.0142825.g003: Comparison of variation within and between mice.(a) The average pairwise weighted UniFrac distances between technical replicates (includes all replicates—biological, extraction, sequencing run, and barcode), within 43 individual mice over less than two weeks (14 days), within four individual mice over 15–31 days, within four individual mice over 32–250 days, and among all different healthy mice. Bar height indicates mean; thin lines at the top indicate the standard error. All categories were significantly different from the technical replicates. ***, p<0.001. NS, non-significant. (b) Average pairwise weighted UniFrac distances between samples collected from the same mice at different times, plotted against time interval between sampling, for up to 14 days. The line represents the linear regression slope. (c) Same as (b) except that time intervals are as long as 236 days.

Mentions: In order to characterize the degree of variation among fecal communities in different mice, we quantified the variation in phylogenetic composition of the microbiota among different mice by calculating the average pairwise weighted UniFrac distance between fecal microbial communities. The average distance between mice was 0.19 (SE = 0.001), which was significantly greater than the average pairwise UniFrac distance among the replicates (0.04, SE = 0.004) (p<0.001) (Fig 3A), indicating that mice have distinct, individualized communities.


Variation in Taxonomic Composition of the Fecal Microbiota in an Inbred Mouse Strain across Individuals and Time.

Hoy YE, Bik EM, Lawley TD, Holmes SP, Monack DM, Theriot JA, Relman DA - PLoS ONE (2015)

Comparison of variation within and between mice.(a) The average pairwise weighted UniFrac distances between technical replicates (includes all replicates—biological, extraction, sequencing run, and barcode), within 43 individual mice over less than two weeks (14 days), within four individual mice over 15–31 days, within four individual mice over 32–250 days, and among all different healthy mice. Bar height indicates mean; thin lines at the top indicate the standard error. All categories were significantly different from the technical replicates. ***, p<0.001. NS, non-significant. (b) Average pairwise weighted UniFrac distances between samples collected from the same mice at different times, plotted against time interval between sampling, for up to 14 days. The line represents the linear regression slope. (c) Same as (b) except that time intervals are as long as 236 days.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643986&req=5

pone.0142825.g003: Comparison of variation within and between mice.(a) The average pairwise weighted UniFrac distances between technical replicates (includes all replicates—biological, extraction, sequencing run, and barcode), within 43 individual mice over less than two weeks (14 days), within four individual mice over 15–31 days, within four individual mice over 32–250 days, and among all different healthy mice. Bar height indicates mean; thin lines at the top indicate the standard error. All categories were significantly different from the technical replicates. ***, p<0.001. NS, non-significant. (b) Average pairwise weighted UniFrac distances between samples collected from the same mice at different times, plotted against time interval between sampling, for up to 14 days. The line represents the linear regression slope. (c) Same as (b) except that time intervals are as long as 236 days.
Mentions: In order to characterize the degree of variation among fecal communities in different mice, we quantified the variation in phylogenetic composition of the microbiota among different mice by calculating the average pairwise weighted UniFrac distance between fecal microbial communities. The average distance between mice was 0.19 (SE = 0.001), which was significantly greater than the average pairwise UniFrac distance among the replicates (0.04, SE = 0.004) (p<0.001) (Fig 3A), indicating that mice have distinct, individualized communities.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus