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C. difficile may be overdiagnosed in adults and is a prevalent commensal in infants

View ORCID ProfilePamela Ferretti, View ORCID ProfileJakob Wirbel, View ORCID ProfileOleksandr M Maistrenko, View ORCID ProfileThea Van Rossum, View ORCID ProfileRenato Alves, View ORCID ProfileAnthony Fullam, View ORCID ProfileWasiu Akanni, View ORCID ProfileChristian Schudoma, Anna Schwarz, View ORCID ProfileRoman Thielemann, Leonie Thomas, View ORCID ProfileStefanie Kandels, View ORCID ProfileRajna Hercog, View ORCID ProfileAnja Telzerow, View ORCID ProfileIvica Letunic, View ORCID ProfileMichael Kuhn, View ORCID ProfileGeorg Zeller, View ORCID ProfileThomas SB Schmidt, View ORCID ProfilePeer Bork
doi: https://doi.org/10.1101/2022.02.16.480740
Pamela Ferretti
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Jakob Wirbel
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Oleksandr M Maistrenko
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
2Royal Netherlands Institute for Sea Research (NIOZ), Department of Marine Microbiology & Biogeochemistry, 1797 SZ, ‘t Horntje (Texel), Netherlands
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Thea Van Rossum
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Renato Alves
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Anthony Fullam
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Wasiu Akanni
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Christian Schudoma
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Anna Schwarz
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Roman Thielemann
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Leonie Thomas
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Stefanie Kandels
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Rajna Hercog
3Genomic Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
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Anja Telzerow
3Genomic Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
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Ivica Letunic
4biobyte solutions GmbH, Bothestr 142, 69126 Heidelberg
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Michael Kuhn
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Georg Zeller
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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Thomas SB Schmidt
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
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  • For correspondence: sebastian.schmidt@embl.de Bork@embl.de
Peer Bork
1European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
5Max Delbrück Centre for Molecular Medicine, Berlin, Germany
6Yonsei Frontier Lab (YFL), Yonsei University, Seoul 03722, South Korea
7Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany
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  • For correspondence: sebastian.schmidt@embl.de Bork@embl.de
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Summary

Clostridioides difficile infection (CDI) is an urgent threat in nosocomial infections, yet its associated microbiome remains poorly characterised. Among 534 metagenomes from 10 public CDI study populations we detected C. difficile in only 30% of samples, yet other toxigenic species with CDI-like symptomatology were prevalent, indicating possible CDI overdiagnosis. Tracking C. difficile across 42,900 metagenomes from 253 public studies, we found that prevalence, abundance and biotic context were age-dependent. C. difficile is a rare taxon associated with reduced diversity in healthy adults, but common and associated with increased diversity in infants. We identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typical of the healthy adult gut microbiome. Overall, C. difficile in healthy infants is associated with multiple indicators of healthy gut microbiome maturation, suggesting that C. difficile is an important commensal in infants and that its asymptomatic carriage in adults depends on microbial context.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Author list and supplemental files updated; title and discussion section revised.

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 4.0 International license.
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Posted October 05, 2022.
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C. difficile may be overdiagnosed in adults and is a prevalent commensal in infants
Pamela Ferretti, Jakob Wirbel, Oleksandr M Maistrenko, Thea Van Rossum, Renato Alves, Anthony Fullam, Wasiu Akanni, Christian Schudoma, Anna Schwarz, Roman Thielemann, Leonie Thomas, Stefanie Kandels, Rajna Hercog, Anja Telzerow, Ivica Letunic, Michael Kuhn, Georg Zeller, Thomas SB Schmidt, Peer Bork
bioRxiv 2022.02.16.480740; doi: https://doi.org/10.1101/2022.02.16.480740
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C. difficile may be overdiagnosed in adults and is a prevalent commensal in infants
Pamela Ferretti, Jakob Wirbel, Oleksandr M Maistrenko, Thea Van Rossum, Renato Alves, Anthony Fullam, Wasiu Akanni, Christian Schudoma, Anna Schwarz, Roman Thielemann, Leonie Thomas, Stefanie Kandels, Rajna Hercog, Anja Telzerow, Ivica Letunic, Michael Kuhn, Georg Zeller, Thomas SB Schmidt, Peer Bork
bioRxiv 2022.02.16.480740; doi: https://doi.org/10.1101/2022.02.16.480740

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