Structural variation in the gut microbiome associates with host health

David Zeevi (), Tal Korem, Anastasia Godneva, Noam Bar, Alexander Kurilshikov, Maya Lotan-Pompan, Adina Weinberger, Jingyuan Fu, Cisca Wijmenga, Alexandra Zhernakova and Eran Segal ()
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David Zeevi: Weizmann Institute of Science
Tal Korem: Weizmann Institute of Science
Anastasia Godneva: Weizmann Institute of Science
Noam Bar: Weizmann Institute of Science
Alexander Kurilshikov: University of Groningen, University Medical Center Groningen, Department of Genetics
Maya Lotan-Pompan: Weizmann Institute of Science
Adina Weinberger: Weizmann Institute of Science
Jingyuan Fu: University of Groningen, University Medical Center Groningen, Department of Genetics
Cisca Wijmenga: University of Groningen, University Medical Center Groningen, Department of Genetics
Alexandra Zhernakova: University of Groningen, University Medical Center Groningen, Department of Genetics
Eran Segal: Weizmann Institute of Science

Nature, 2019, vol. 568, issue 7750, 43-48

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1065-y

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