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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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Variation in fecal bacterial diversity over time.Relative taxa abundances are shown for four mice sampled over 200 days. Timepoints are shown in chronological order for each mouse. The column on the right shows the average of all 46 samples. (a) Relative abundances of phyla and classes. (b) Heatmap showing the relative abundances of the 400 most abundant OTUs in the four mice sampled for more than 200 days. Phylum and class assignments of these OTUs are shown along the right side of the heatmap. Key on the right indicates the correspondence of the gray values to the relative OTU abundance.
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pone.0142825.g002: Variation in fecal bacterial diversity over time.Relative taxa abundances are shown for four mice sampled over 200 days. Timepoints are shown in chronological order for each mouse. The column on the right shows the average of all 46 samples. (a) Relative abundances of phyla and classes. (b) Heatmap showing the relative abundances of the 400 most abundant OTUs in the four mice sampled for more than 200 days. Phylum and class assignments of these OTUs are shown along the right side of the heatmap. Key on the right indicates the correspondence of the gray values to the relative OTU abundance.

Mentions: To determine the variation in individual mice over time we sampled 4 mice for over 200 days. We found large differences in the relative abundance of the major phyla within an individual mouse; for example, in mouse II_D_14 the relative abundance of Bacteroidetes ranged from less than 10% to greater than 90% (Fig 2A). We also found shifts in abundance at the OTU level within a mouse over time, including an increase in some Bacteroidetes OTUs (Fig 2B). To determine if the overall number of OTUs increased over time, we calculated the number of OTUs present in all samples from these four time courses (data rarefied to 5400 reads per sample). We found that the number of OTUs increased over the first 50 days (slope = 3.5 +/- 1.2; p-value = 0.005) (S4A Fig) When the data were separated by mouse, we found that this trend was significant in three of the four mice, with the other one having a positive but non-significant slope (S4B Fig). Measures of alpha diversity and evenness showed similar patterns (S4C–S4H Fig).


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)

Variation in fecal bacterial diversity over time.Relative taxa abundances are shown for four mice sampled over 200 days. Timepoints are shown in chronological order for each mouse. The column on the right shows the average of all 46 samples. (a) Relative abundances of phyla and classes. (b) Heatmap showing the relative abundances of the 400 most abundant OTUs in the four mice sampled for more than 200 days. Phylum and class assignments of these OTUs are shown along the right side of the heatmap. Key on the right indicates the correspondence of the gray values to the relative OTU abundance.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0142825.g002: Variation in fecal bacterial diversity over time.Relative taxa abundances are shown for four mice sampled over 200 days. Timepoints are shown in chronological order for each mouse. The column on the right shows the average of all 46 samples. (a) Relative abundances of phyla and classes. (b) Heatmap showing the relative abundances of the 400 most abundant OTUs in the four mice sampled for more than 200 days. Phylum and class assignments of these OTUs are shown along the right side of the heatmap. Key on the right indicates the correspondence of the gray values to the relative OTU abundance.
Mentions: To determine the variation in individual mice over time we sampled 4 mice for over 200 days. We found large differences in the relative abundance of the major phyla within an individual mouse; for example, in mouse II_D_14 the relative abundance of Bacteroidetes ranged from less than 10% to greater than 90% (Fig 2A). We also found shifts in abundance at the OTU level within a mouse over time, including an increase in some Bacteroidetes OTUs (Fig 2B). To determine if the overall number of OTUs increased over time, we calculated the number of OTUs present in all samples from these four time courses (data rarefied to 5400 reads per sample). We found that the number of OTUs increased over the first 50 days (slope = 3.5 +/- 1.2; p-value = 0.005) (S4A Fig) When the data were separated by mouse, we found that this trend was significant in three of the four mice, with the other one having a positive but non-significant slope (S4B Fig). Measures of alpha diversity and evenness showed similar patterns (S4C–S4H Fig).

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