Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model
Open accessAbstract
Maternal transmission and cage effects are powerful confounding factors in microbiome studies. To assess the consequences of cage microenvironment on the mouse gut microbiome, two groups of germ-free (GF) wild-type (WT) mice, one gavaged with a microbiota harvested from adult WT mice and another allowed to acquire the microbiome from the cage microenvironment, were monitored using Illumina 16S rRNA sequencing over a period of 8 weeks. Our results revealed that cage effects in WT mice moved from GF to specific pathogen free (SPF) conditions take several weeks to develop and are not eliminated by the initial gavage treatment. Initial gavage influenced, but did not eliminate a successional pattern in which Proteobacteria became less abundant over time. An analysis in which 16S rRNA sequences are mapped to the closest sequenced whole genome suggests that the functional potential of microbial genomes changes significantly over time shifting from an emphasis on pathogenesis and motility early in community assembly to metabolic processes at later time points. Functionally, mice allowed to naturally acquire a microbial community from their cage, but not mice gavaged with a common biome, exhibit a cage effect in Dextran Sulfate Sodium-induced inflammation. Our results argue that while there are long-term effects of the founding community, these effects are mitigated by cage microenvironment and successional community assembly over time, which must both be explicitly considered in the interpretation of microbiome mouse experiments.
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Technical variability between studies in microbiome measurements can sometimes exceed biological effects.
“Inter-study technical variability in microbiome measurements can sometimes, for example, outweigh biological effects6–9.”
From Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium (2017) · cites this paper as [8]
DNA extraction protocols are a known source of variation in microbial community characterization experiments.
“DNA extraction protocols are a known source of variation between microbial community characterization experiments7–9.”
From Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium (2017) · cites this paper as [8]
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- Authors
- McCafferty, J., Mühlbauer, M., Gharaibeh, R. Z., Arthur, J. C., Perez-Chanona, E., Sha, W., Jobin, C., & Fodor, A. A.
- Affiliations
- University of North Carolina at Charlotte (US)
- University of North Carolina at Chapel Hill (US)
- Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill , Chapel Hill, NC, USA
- Corresponding author
- Jobin, Christian
- Fodor, Anthony A
- ORCID
- Venue
- The ISME Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-07-04
- Volume
- 7
- Issue
- 11
- Pages
- 2116-2125
- ISSN
- 1751-7362 (ISSN-L)
- 1751-7370
- PMC
- PMC3806260
- OpenAlex
- W2061219514
- Cited by
- 259
- References
- 32
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 17 · 2023: 18 · 2022: 19 · 2021: 40 · 2020: 28 · 2019: 29 · 2018: 25 · 2017: 23 · 2016: 15 · 2015: 12 · 2014: 12 · 2013: 3
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The ISME Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Crohn's and Colitis Foundation of America (P30 DK034987)
- Crohn's and Colitis Foundation
- National Institutes of Health (DK034987)
- U.S. Public Health Service (P40 R018603)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK47700, R01 DK73338, R01DK047700, R01DK073338, P30DK034987)
- Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill (P30 DK 034987)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- cage effect, microbial community assembly, mouse gut microbiome, germ-free mice, gavage, founder effect, microbial succession, Proteobacteria, DSS-induced colitis
- MeSH terms
- Animals, Environmental Microbiology, Housing, Animal, RNA, Ribosomal, 16S, Time Factors, Founder Effect, Gastrointestinal Tract, Biodiversity, Mice
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