Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status

Abstract Ruminococcus gnavus is a gut bacterium found in > 90% of healthy individuals, but its increased abundance is also associated with chronic inflammatory diseases, particularly Crohn’s disease. Nevertheless, its global distribution and intraspecies genomic variation remain understudied. By...

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Main Authors: S. Nooij, N. Plomp, I. M. J. G. Sanders, L. Schout, A. E. van der Meulen, E. M. Terveer, J. M. Norman, N. Karcher, M. F. Larralde, R. H. A. M. Vossen, S. L. Kloet, K. N. Faber, H. J. M. Harmsen, G. F. Zeller, E. J. Kuijper, W. K. Smits, Q. R. Ducarmon
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56449-x
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author S. Nooij
N. Plomp
I. M. J. G. Sanders
L. Schout
A. E. van der Meulen
E. M. Terveer
J. M. Norman
N. Karcher
M. F. Larralde
R. H. A. M. Vossen
S. L. Kloet
K. N. Faber
H. J. M. Harmsen
G. F. Zeller
E. J. Kuijper
W. K. Smits
Q. R. Ducarmon
author_facet S. Nooij
N. Plomp
I. M. J. G. Sanders
L. Schout
A. E. van der Meulen
E. M. Terveer
J. M. Norman
N. Karcher
M. F. Larralde
R. H. A. M. Vossen
S. L. Kloet
K. N. Faber
H. J. M. Harmsen
G. F. Zeller
E. J. Kuijper
W. K. Smits
Q. R. Ducarmon
author_sort S. Nooij
collection DOAJ
description Abstract Ruminococcus gnavus is a gut bacterium found in > 90% of healthy individuals, but its increased abundance is also associated with chronic inflammatory diseases, particularly Crohn’s disease. Nevertheless, its global distribution and intraspecies genomic variation remain understudied. By surveying 12,791 gut metagenomes, we recapitulated known associations with metabolic diseases and inflammatory bowel disease. We uncovered a higher prevalence and abundance of R. gnavus in Westernized populations and observed bacterial relative abundances up to 83% in newborns. Next, we built a resource of R. gnavus isolates (N = 45) from healthy individuals and Crohn’s disease patients and generated complete R. gnavus genomes using PacBio circular consensus sequencing. Analysis of these genomes and publicly available high-quality draft genomes (N = 333 genomes) revealed multiple clades which separated Crohn’s-derived isolates from healthy-derived isolates. Presumed R. gnavus virulence factors could not explain this separation. Bacterial genome-wide association study revealed that Crohn’s-derived isolates were enriched in genes related to mobile elements and mucin foraging. Together, we present a large R. gnavus resource that will be available to the scientific community and provide novel biological insights into the global distribution and genomic variation of R. gnavus.
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spelling doaj-art-9e53cf560f804ee59a7e2e44dedc614e2025-02-02T12:33:03ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-56449-xMetagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health statusS. Nooij0N. Plomp1I. M. J. G. Sanders2L. Schout3A. E. van der Meulen4E. M. Terveer5J. M. Norman6N. Karcher7M. F. Larralde8R. H. A. M. Vossen9S. L. Kloet10K. N. Faber11H. J. M. Harmsen12G. F. Zeller13E. J. Kuijper14W. K. Smits15Q. R. Ducarmon16Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center GroningenLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, Leiden University Medical CenterLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterVedanta Biosciences, Inc., CambridgeMolecular Systems Biology Unit, European Molecular Biology LaboratoryLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterLeiden Genome Technology Center, Leiden University Medical CenterLeiden Genome Technology Center, Leiden University Medical CenterDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center GroningenDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center GroningenLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterLeiden University Center for Infectious Diseases (LUCID), Leiden University Medical CenterAbstract Ruminococcus gnavus is a gut bacterium found in > 90% of healthy individuals, but its increased abundance is also associated with chronic inflammatory diseases, particularly Crohn’s disease. Nevertheless, its global distribution and intraspecies genomic variation remain understudied. By surveying 12,791 gut metagenomes, we recapitulated known associations with metabolic diseases and inflammatory bowel disease. We uncovered a higher prevalence and abundance of R. gnavus in Westernized populations and observed bacterial relative abundances up to 83% in newborns. Next, we built a resource of R. gnavus isolates (N = 45) from healthy individuals and Crohn’s disease patients and generated complete R. gnavus genomes using PacBio circular consensus sequencing. Analysis of these genomes and publicly available high-quality draft genomes (N = 333 genomes) revealed multiple clades which separated Crohn’s-derived isolates from healthy-derived isolates. Presumed R. gnavus virulence factors could not explain this separation. Bacterial genome-wide association study revealed that Crohn’s-derived isolates were enriched in genes related to mobile elements and mucin foraging. Together, we present a large R. gnavus resource that will be available to the scientific community and provide novel biological insights into the global distribution and genomic variation of R. gnavus.https://doi.org/10.1038/s41467-025-56449-x
spellingShingle S. Nooij
N. Plomp
I. M. J. G. Sanders
L. Schout
A. E. van der Meulen
E. M. Terveer
J. M. Norman
N. Karcher
M. F. Larralde
R. H. A. M. Vossen
S. L. Kloet
K. N. Faber
H. J. M. Harmsen
G. F. Zeller
E. J. Kuijper
W. K. Smits
Q. R. Ducarmon
Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status
Nature Communications
title Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status
title_full Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status
title_fullStr Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status
title_full_unstemmed Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status
title_short Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status
title_sort metagenomic global survey and in depth genomic analyses of ruminococcus gnavus reveal differences across host lifestyle and health status
url https://doi.org/10.1038/s41467-025-56449-x
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