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Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

View ORCID ProfileAnastasia Gulyaeva, View ORCID ProfileSanzhima Garmaeva, Renate A.A.A. Ruigrok, View ORCID ProfileDaoming Wang, View ORCID ProfileNiels P. Riksen, View ORCID ProfileMihai G. Netea, View ORCID ProfileCisca Wijmenga, View ORCID ProfileRinse K. Weersma, View ORCID ProfileJingyuan Fu, View ORCID ProfileArnau Vich Vila, View ORCID ProfileAlexander Kurilshikov, View ORCID ProfileAlexandra Zhernakova
doi: https://doi.org/10.1101/2021.06.01.446427
Anastasia Gulyaeva
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
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  • ORCID record for Anastasia Gulyaeva
  • For correspondence: a.gulyaeva@umcg.nl a.zhernakova@umcg.nl
Sanzhima Garmaeva
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
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  • ORCID record for Sanzhima Garmaeva
Renate A.A.A. Ruigrok
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
2Department of Gastroenterology and Hepatology, University Medical Center Groningen, the Netherlands
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Daoming Wang
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
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  • ORCID record for Daoming Wang
Niels P. Riksen
3Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
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  • ORCID record for Niels P. Riksen
Mihai G. Netea
3Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
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  • ORCID record for Mihai G. Netea
Cisca Wijmenga
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
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  • ORCID record for Cisca Wijmenga
Rinse K. Weersma
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
2Department of Gastroenterology and Hepatology, University Medical Center Groningen, the Netherlands
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Jingyuan Fu
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
4Department of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands
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Arnau Vich Vila
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
2Department of Gastroenterology and Hepatology, University Medical Center Groningen, the Netherlands
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Alexander Kurilshikov
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
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Alexandra Zhernakova
1Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
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  • ORCID record for Alexandra Zhernakova
  • For correspondence: a.gulyaeva@umcg.nl a.zhernakova@umcg.nl
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Summary

The crAss-like phages are a diverse group of related viruses that includes one of the most abundant viruses of the human gut. To explore their diversity and functional role in human population and clinical cohorts, we analyzed gut metagenomic data collected from more than 2000 individuals from the Netherlands. We discovered 125 novel species-level and 32 novel genus-level clusters of crAss-like phages, all belonging to five previously recognized groups associated with the human gut. Analysis of their genomic features revealed that closely related crAss-like phages can possess strikingly divergent regions responsible for transcription, presumably acquired through recombination. Prediction of crAss-like phage hosts pointed primarily to bacteria of the phylum Bacteroidetes, consistent with previous reports. Finally, we explored the temporal stability of crAss-like phages over a 4-year period and identified associations between the abundance of crAss-like phages and several human phenotypes, including depletion of crAss-like phages in inflammatory bowel disease patients.

Highlights

  • 125 tentative new species of crAss-like phages were discovered

  • Closely related crAss-like phages often possess highly divergent transcription gene modules possibly acquired via recombination

  • CrAss-like fraction of the human gut virome remains relatively stable over the period of 4 years

  • Prevalence of crAss-like phages in the human gut is associated with several metabolic, dietary and health phenotypes

  • Gut crAss-like phages are depleted in inflammatory bowel disease patients

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 06, 2021.
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Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts
Anastasia Gulyaeva, Sanzhima Garmaeva, Renate A.A.A. Ruigrok, Daoming Wang, Niels P. Riksen, Mihai G. Netea, Cisca Wijmenga, Rinse K. Weersma, Jingyuan Fu, Arnau Vich Vila, Alexander Kurilshikov, Alexandra Zhernakova
bioRxiv 2021.06.01.446427; doi: https://doi.org/10.1101/2021.06.01.446427
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Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts
Anastasia Gulyaeva, Sanzhima Garmaeva, Renate A.A.A. Ruigrok, Daoming Wang, Niels P. Riksen, Mihai G. Netea, Cisca Wijmenga, Rinse K. Weersma, Jingyuan Fu, Arnau Vich Vila, Alexander Kurilshikov, Alexandra Zhernakova
bioRxiv 2021.06.01.446427; doi: https://doi.org/10.1101/2021.06.01.446427

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