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Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function
Jocelyn M Choo1, Paul J Trim2, Lex E X Leong1
1Infection and Immunity Theme, South Australian Health and Medical Research Institute, AdelaideSA, Australia.
Abstract:
Inbred mice are used to investigate many aspects of human physiology, including susceptibility to disease and response to therapies. Despite increasing evidence that the composition and function of the murine intestinal microbiota can substantially influence a broad range of experimental outcomes, relatively little is known about microbiome dynamics within experimental mouse populations. We investigated changes in the intestinal microbiome between C57BL/6J mice spanning six generations (assessed at generations 1, 2, 3, and 6), following their introduction to a stringently controlled facility. Fecal microbiota composition and function were assessed by 16S rRNA gene amplicon sequencing and liquid chromatography mass spectrometry, respectively. Significant divergence of the intestinal microbiota between founder and second generation mice, as well as continuing inter-generational variance, was observed. Bacterial taxa whose relative abundance changed significantly through time included Akkermansia, Turicibacter, and Bifidobacterium (p < 0.05), all of which are recognized as having the potential to substantially influence host physiology. Shifts in microbiota composition were mirrored by corresponding differences in the fecal metabolome (r = 0.57, p = 0.0001), with notable differences in levels of tryptophan pathway metabolites and amino acids, including glutamine, glutamate and aspartate. We related the magnitude of changes in the intestinal microbiota and metabolome characteristics during acclimation to those observed between populations housed in separate facilities, which differed in regards to husbandry, barrier conditions and dietary intake. The microbiome variance reported here has implications for experimental reproducibility, and as a consequence, experimental design and the interpretation of research outcomes across wide range of contexts.
Insights
The mouse intestinal microbiome changes significantly across generations in a controlled facility, impacting experimental results. Understanding these microbiome dynamics is crucial for reproducible research.
Area of Science:
- Microbiology
- Genomics
- Metabolomics
Background:
- Inbred mice are vital models for human physiology research.
- Murine intestinal microbiota significantly impacts experimental outcomes.
- Microbiome dynamics in experimental mouse populations are poorly understood.
Purpose of the Study:
- Investigate changes in the intestinal microbiome across six generations of C57BL/6J mice.
- Assess the impact of a controlled facility environment on microbiome composition and function.
- Relate microbiome shifts to experimental reproducibility.
Main Methods:
- 16S rRNA gene amplicon sequencing for fecal microbiota composition.
- Liquid chromatography-mass spectrometry for fecal metabolome analysis.
- Longitudinal assessment across multiple mouse generations.
Main Results:
- Significant divergence in intestinal microbiota observed between founder and second-generation mice.
- Inter-generational variance in bacterial taxa (Akkermansia, Turicibacter, Bifidobacterium) and fecal metabolome.
- Microbiome and metabolome shifts correlated with facility acclimation and housing conditions.
Conclusions:
- Mouse intestinal microbiome composition and function change across generations.
- These microbiome dynamics introduce variance impacting experimental reproducibility.
- Consideration of microbiome changes is essential for robust experimental design and interpretation.
