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Structural variation in the gut microbiome associates with host health
Open accessAbstract
Differences in the presence of even a few genes between otherwise identical bacterial strains may result in critical phenotypic differences. Here we systematically identify microbial genomic structural variants (SVs) and find them to be prevalent in the human gut microbiome across phyla and to replicate in different cohorts. SVs are enriched for CRISPR-associated and antibiotic-producing functions and depleted from housekeeping genes, suggesting that they have a role in microbial adaptation. We find multiple associations between SVs and host disease risk factors, many of which replicate in an independent cohort. Exploring genes that are clustered in the same SV, we uncover several possible mechanistic links between the microbiome and its host, including a region in Anaerostipes hadrus that encodes a composite inositol catabolism-butyrate biosynthesis pathway, the presence of which is associated with lower host metabolic disease risk. Overall, our results uncover a nascent layer of variability in the microbiome that is associated with microbial adaptation and host health.
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“recent findings have identified an elementary layer of variability in the microbiome identified as microbial genomic structural variants (the term pertaining to the existence of a few genes which are different between otherwise identical bacterial strains) that are specifically unique to the host microbiota and demonstrate a strong association with host metabolic health (Zeevi et al., 2019).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Zeevi et al., 2019
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“We therefore tested for specific bacterial genomic regions that may be responsible for the variation in metabolic output between the groups using the recently described method that associates structurally variable genomic regions to metabolite abundances (SV association) (Zeevi et al., 2019).”
Self-citationA reference map of potential determinants for the human serum metabolome
Bar, N., Korem, T., Weissbrod, O., Zeevi, D., Rothschild, D., Leviatan, S., Kosower, N., Lotan‐Pompan, M., Weinberger, A., Roy, C. I. L., et al. (2020) · Nature · doi:10.1038/s41586-020-2896-2 · Cited by 440
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Metadata
- Authors
- Zeevi, D., Korem, T., Godneva, A., Bar, N., Kurilshikov, A., Lotan-Pompan, M., Weinberger, A., Fu, J., Wijmenga, C., Zhernakova, A., & Segal, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Columbia University Irving Medical Center (US)
- University Medical Center Groningen (NL)
- Corresponding author
- Zeevi, David
- Segal, Eran
- ORCID
- Venue
- Nature
- Published
- 2019-03-27
- Volume
- 568
- Issue
- 7750
- Pages
- 43-48
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2924485771
- Cited by
- 351
- References
- 53
- Citations by year
- 2026: 33 · 2025: 40 · 2024: 58 · 2023: 46 · 2022: 55 · 2021: 51 · 2020: 45 · 2019: 23
- FWCI
- 14.39
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- James S. McDonnell Foundation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.13.013, 016.Vidi.178.056)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, structural variants, bacterial genomes, antibiotic production, Anaerostipes hadrus, metabolic disorders, host-microbe interactions, bacterial adaptation
- MeSH terms
- Gastrointestinal Microbiome, Host Microbial Interactions, Adaptation, Physiological, Bacteria, Butyrates, Disease Susceptibility, Eubacterium, Feces, Genes, Bacterial, Health, Humans, Inositol, Risk Factors, Genetic Variation, Cohort Studies, Ecosystem, Microbial Viability, Metagenomics
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