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Setting higher standards for reports of microbial species in human cancers

Nature Cancer (2026)Cite this article

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Abstract

The presence of microbiota in human tumors has been reported widely based on bioinformatic analyses of DNA sequencing datasets; however, the source of microbial sequences in atypical anatomical sites is challenging to validate, as these could derive from sampling, storage, handling and processing of samples, similar to what has been described in studies of ancient DNA. Contamination of microbial reference genomes can also be a source of microbial signals, causing misclassification of human reads. Here, we overview the required quality controls and validation approaches and summarize optimal practices to improve the rigor and standards of tumor microbiome studies.

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Fig. 1: Contamination and artefacts obscure true microbial signals in cancer microbiome studies.

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Acknowledgements

This study was supported by a National Medical Research Council grant OFYIRG21nov-0024 to M.C., a National Institutes of Health grant R35-GM130151 to S.L.S., a National Research Foundation Investigatorship grant NRFI09-0015 to N.N. and a Spinoza grant from De Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) to J.N.

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Author notes

  1. These authors contributed equally: Steven L. Salzberg, Minghao Chia.

Authors and Affiliations

  1. Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA

    Steven L. Salzberg

  2. Departments of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Steven L. Salzberg

  3. Departments of Computer Science, Johns Hopkins University, Baltimore, MD, USA

    Steven L. Salzberg

  4. Departments of Biostatistics, Johns Hopkins University, Baltimore, MD, USA

    Steven L. Salzberg

  5. Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore

    Minghao Chia & Niranjan Nagarajan

  6. Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore

    Minghao Chia

  7. Marshall Centre, School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia

    Alfred Tay & Barry Marshall

  8. Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

    Noel F.C.C. de Miranda, Vincent Smit & Jelle Wesseling

  9. Medical & Research Director Center of Early Cancer Detection, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Jelle Wesseling

  10. Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

    Jelle Wesseling

  11. Department of Pathology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Jelle Wesseling

  12. Department of Data Science, Dana Faber Cancer Institute, Boston, MA, USA

    Rafael Irizarry

  13. Centre for Ancient Environmental Genomics and The Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark

    Eske Willerslev

  14. Department of Genetics, University of Cambridge, Cambridge, UK

    Eske Willerslev

  15. MARUM, University of Bremen, Bremen, Germany

    Eske Willerslev

  16. Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands

    Jacques Neefjes

  17. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Niranjan Nagarajan

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Contributions

Conceptualization: S.L.S., M.C., J.N., N.N.; data analysis: M.C., N.N.; writing, original draft: S.L.S., M.C., J.N., N.N.; writing, review and editing: S.L.S., M.C., J.N., N.N., A.T., N.F.C.C.d.M., V.S., J.W., R.I., B.M., E.W.

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Correspondence to Steven L. Salzberg, Jacques Neefjes or Niranjan Nagarajan.

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Salzberg, S.L., Chia, M., Tay, A. et al. Setting higher standards for reports of microbial species in human cancers. Nat Cancer (2026). https://doi.org/10.1038/s43018-026-01121-6

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