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Nature. 2019 Apr;568(7750):43-48. doi: 10.1038/s41586-019-1065-y. Epub 2019 Mar 27.

Structural variation in the gut microbiome associates with host health.

Author information

1
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. dzeevi@rockefeller.edu.
2
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. dzeevi@rockefeller.edu.
3
Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA. dzeevi@rockefeller.edu.
4
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
5
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
6
Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
7
Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA.
8
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
9
University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, The Netherlands.
10
Department of Immunology, K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
11
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. eran.segal@weizmann.ac.il.
12
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. eran.segal@weizmann.ac.il.

Abstract

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.

PMID:
30918406
DOI:
10.1038/s41586-019-1065-y

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