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Structural variation in the gut microbiome associates with host health

Author

Listed:
  • David Zeevi

    (Weizmann Institute of Science
    Weizmann Institute of Science
    The Rockefeller University)

  • Tal Korem

    (Weizmann Institute of Science
    Weizmann Institute of Science
    Columbia University Irving Medical Center
    Columbia University Irving Medical Center)

  • Anastasia Godneva

    (Weizmann Institute of Science
    Weizmann Institute of Science)

  • Noam Bar

    (Weizmann Institute of Science
    Weizmann Institute of Science)

  • Alexander Kurilshikov

    (University of Groningen, University Medical Center Groningen, Department of Genetics)

  • Maya Lotan-Pompan

    (Weizmann Institute of Science
    Weizmann Institute of Science)

  • Adina Weinberger

    (Weizmann Institute of Science
    Weizmann Institute of Science)

  • Jingyuan Fu

    (University of Groningen, University Medical Center Groningen, Department of Genetics
    University Medical Center Groningen, Department of Pediatrics)

  • Cisca Wijmenga

    (University of Groningen, University Medical Center Groningen, Department of Genetics
    K.G. Jebsen Coeliac Disease Research Centre, University of Oslo)

  • Alexandra Zhernakova

    (University of Groningen, University Medical Center Groningen, Department of Genetics)

  • Eran Segal

    (Weizmann Institute of Science
    Weizmann Institute of Science)

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.

Suggested Citation

  • David Zeevi & Tal Korem & Anastasia Godneva & Noam Bar & Alexander Kurilshikov & Maya Lotan-Pompan & Adina Weinberger & Jingyuan Fu & Cisca Wijmenga & Alexandra Zhernakova & Eran Segal, 2019. "Structural variation in the gut microbiome associates with host health," Nature, Nature, vol. 568(7750), pages 43-48, April.
    • Handle: RePEc:nat:nature:v:568:y:2019:i:7750:d:10.1038_s41586-019-1065-y
    DOI: 10.1038/s41586-019-1065-y
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    Citations

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    Cited by:

    1. Rohan Maddamsetti & Yi Yao & Teng Wang & Junheng Gao & Vincent T. Huang & Grayson S. Hamrick & Hye-In Son & Lingchong You, 2024. "Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Liang Chen & Na Zhao & Jiabao Cao & Xiaolin Liu & Jiayue Xu & Yue Ma & Ying Yu & Xuan Zhang & Wenhui Zhang & Xiangyu Guan & Xiaotong Yu & Zhipeng Liu & Yanqun Fan & Yang Wang & Fan Liang & Depeng Wang, 2022. "Short- and long-read metagenomics expand individualized structural variations in gut microbiomes," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Gina Paola Rodriguez-Castaño & Federico E Rey & Alejandro Caro-Quintero & Alejandro Acosta-González, 2020. "Gut-derived Flavonifractor species variants are differentially enriched during in vitro incubation with quercetin," PLOS ONE, Public Library of Science, vol. 15(12), pages 1-21, December.
    4. Jingqiu Liao & Liat Shenhav & Julia A. Urban & Myrna Serrano & Bin Zhu & Gregory A. Buck & Tal Korem, 2023. "Microdiversity of the vaginal microbiome is associated with preterm birth," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Rong Liu & You Zou & Wei-Quan Wang & Jun-Hong Chen & Lei Zhang & Jia Feng & Ji-Ye Yin & Xiao-Yuan Mao & Qing Li & Zhi-Ying Luo & Wei Zhang & Dao-Ming Wang, 2023. "Gut microbial structural variation associates with immune checkpoint inhibitor response," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Alan Le Goallec & Braden T Tierney & Jacob M Luber & Evan M Cofer & Aleksandar D Kostic & Chirag J Patel, 2020. "A systematic machine learning and data type comparison yields metagenomic predictors of infant age, sex, breastfeeding, antibiotic usage, country of origin, and delivery type," PLOS Computational Biology, Public Library of Science, vol. 16(5), pages 1-21, May.

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