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Genetic and environmental control of host-gut microbiota interactions
Open accessAbstract
Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high-resolution association mapping. Using a SNP-based approach with a linear mixed model, we estimated the heritability of microbiota composition. We conclude that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high-fat, high-sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, A×B19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain A×B19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host-microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publicly available data provide a resource for future studies.
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“Recent multi-omic studies [31, 33, 34] have revealed an impact of gut microbiota on host responses to dietary challenge and on epigenetic programming.”
From Multi-omics approaches to disease (2017) · cites this paper as [33]
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Metadata
- Authors
- Org, E., Parks, B. W., Joo, J. W. J., Emert, B., Schwartzman, W., Kang, E. Y., Mehrabian, M., Pan, C., Knight, R., Gunsalus, R., Drake, T. A., Eskin, E., & Lusis, A. J.
- Affiliations
- University of California, Los Angeles (US)
- University of California San Diego (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-08-10
- Volume
- 25
- Issue
- 10
- Pages
- 1558-1569
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC4579341
- OpenAlex
- W2161377204
- Cited by
- 381
- References
- 70
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 28 · 2023: 34 · 2022: 36 · 2021: 75 · 2020: 41 · 2019: 27 · 2018: 38 · 2017: 36 · 2016: 38 · 2015: 3
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (HL028481, HL30568, DK094311)
- UCLA Iris Cantor Women's Health Center
- MOBILITAS Postdoctoral Research (MJD252, 330381)
- NIH (T32-HD07228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota composition, inbred mouse strains, association mapping, cross-fostering, high-fat high-sugar diet, Akkermansia muciniphila, obesity, insulin resistance, plasma lipids, candidate genes
- MeSH terms
- Gastrointestinal Microbiome, Animals, Diet, Environment, Female, Male, Mice, Inbred Strains, Obesity, RNA, Ribosomal, 16S, Sucrose, Heredity, Mice, Genome-Wide Association Study, Diet, High-Fat
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