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  • Perspective
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The new microbiome on the block: challenges and opportunities of using human tumor sequencing data to study microbes

Nature Methods volume 22, pages 1788–1799 (2025) Cite this article

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Abstract

Microbes within tumors have been recognized and experimentally related to oncogenesis, tumor growth, metastasis and therapeutic responsiveness. Studying the tumor microbiome presents difficulties, as early indications suggest that microbe populations are low in abundance, sparse and highly heterogeneous. Disparate results from computational profiling of the tumor microbiome have cast doubt on the premise of microbes in tumors. Yet decades of experimental evidence support the presence of tumor microbes, at least in a limited number of tumor types. In this Perspective, we discuss the importance of iteratively improving microbe-targeted sequencing techniques, established analytical pipelines, robust computational tools and solid validations to address current challenges and fill existing knowledge gaps. The vast amount of human tumor sequencing data available could greatly enhance systematic investigations of microbiome–tumor interactions with methods to quantify the composition of the tumor microbiome accurately.

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Fig. 1: Evidence and technologies emerging for the tumor microbiome.
The alternative text for this image may have been generated using AI.
Fig. 2: A general and typical computational framework for host tumor microbiome analysis.
The alternative text for this image may have been generated using AI.

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Acknowledgements

Q.M. is supported by NIH R01GM152585 and P01AI177687. Z.L. is supported by the NIH (P01CA278732). D.S. is supported by the NIH (K01AG070310, R01CA248741 and R21CA294050), an American Lung Association Innovator Award (1046611) and an American Cancer Society Research Scholar Award (RSG-23-1023205). S.D. is supported in part by the NIH (R35GM149224, R01GM129066 and P01CA250957) and a New Jersey Commission for Cancer Research grant (COCR25RBG003). S.J. is supported by NIH DP2AI171139, R01AI149672 and U24CA224331, the Gilead’s Research Scholars Program in Hematologic Malignancies, the Bill & Melinda Gates Foundation (INV-002704), a Broad Next Generation Award, the Dye Family Foundation and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center. This work was also supported by the Pelotonia Institute of Immuno-Oncology. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Pelotonia Institute of Immuno-Oncology or the NIH. We extend our gratitude to C. Zimmer for his outstanding series of articles and interviews on cancer microbes, which were published in the New York Times. We also thank G. Gürsoy for sharing thoughts about their work in data sanitization and for pointing out the critical paper.

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  1. Deceased: Charis Eng.

Authors and Affiliations

  1. Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH, USA

    Yingjie Li, Anjun Ma & Qin Ma

  2. Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, Columbus, OH, USA

    Yingjie Li, Anjun Ma, Zihai Li, Daniel Spakowicz & Qin Ma

  3. Division of Infectious Disease, Center for Data Science, Rutgers University, New Jersey Medical School, Newark, NJ, USA

    Evan Johnson

  4. Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Charis Eng

  5. Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA

    Subhajyoti De

  6. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Sizun Jiang

  7. Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA

    Sizun Jiang

  8. Division of Medical Oncology, Department of Internal Medicine, the Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Daniel Spakowicz

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Contributions

Q.M. and D.S. conceptualized the work. Y.L. researched literature and data. Y.L. and A.M. wrote the original draft and created the figures. E.J., C.E., S.D., S.J. and Z.L. critically revised the manuscript. Y.L., A.M., D.S. and Q.M. finalized the manuscript.

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Correspondence to Daniel Spakowicz or Qin Ma.

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Competing interests

S.J. is a cofounder of Elucidate Bio, serves on its board of directors and scientific advisory board and has received research support from Roche and Novartis. The other authors declare no competing interests.

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Nature Methods thanks Georg Zeller and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Madhura Mukhopadhyay, in collaboration with the Nature Methods team.

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Li, Y., Ma, A., Johnson, E. et al. The new microbiome on the block: challenges and opportunities of using human tumor sequencing data to study microbes. Nat Methods 22, 1788–1799 (2025). https://doi.org/10.1038/s41592-025-02807-y

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