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Reply to: Revisiting the intrinsic mycobiome in pancreatic cancer

Nature volume 620, pages E7–E9 (2023)Cite this article

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The Original Article was published on 02 August 2023

replying to: A. A. Fletcher et al. Nature https://doi.org/10.1038/s41586-023-06292-1 (2023)

In their reanalysis of our human dataset, Fletcher et al. found no statistical significance in the mycobiome of pancreatic ductal adenocarcinoma (PDAC) compared with healthy pancreas using a different version of QIIME, that is, QIIME2, and DADA2 (ref. 1). In our original study, we demonstrated fungal dysbiosis in human and mouse PDAC in the pancreas and gut, including predominance of Malassezia in the transformed pancreatic tissues2. Although the differences between our results and Fletcher et al. may relate to the analytical techniques used, we do not concur with their conclusion questioning a role for fungi in pancreatic oncogenesis1,2. Our findings have since been reproduced in multiple other basic and translational studies and have specifically confirmed the importance of Malassezia3,4,5,6,7. Collectively, our data established a link between PDAC progression and fungal dysbiosis that spurred this area of cancer research.

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Fig. 1: Relative distribution of mock communities of three ATCC fungal cultures as sequenced by ITS sequencing on Ilumina MiSeq (v3 chemistry).
Fig. 2: Abundance of fungal genera in human PDAC tumours.

Data availability

The sequence datasets analysed by QIIME2 in this article are publicly available in the NCBI BioProject database, under the accession number PRJNA557226. Sequencing data analysis scripts and the R code used for downstream analysis and generating the plots are available at GitHub (https://github.com/Fangxi-Xu/Pancan).

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Acknowledgements

This work was supported by the National Institutes of Health, US grants RO1 CA206105 (to D.S.), DOD W81XWH-19-1-0605 (to D.S.) and R41 CA250892 (to D.S.).

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Author notes

  1. These authors contributed equally: Smruti Pushalkar, George Miller

Authors and Affiliations

  1. Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA

    Fangxi Xu & Deepak Saxena

  2. Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA

    Deepak Saxena

  3. Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA

    Deepak Saxena

  4. NYU Center for Genomics and Systems Biology, New York, NY, USA

    Smruti Pushalkar

  5. Trinity Health of New England, Waterbury, CT, USA

    George Miller

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Contributions

D.S., S.P. and G.M. wrote the Reply. F.X. and S.P. analysed the data and designed the figures. All authors verified the content.

Corresponding author

Correspondence to George Miller.

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Competing interests

D.S. is a co-founder of PeriomicsCare LLC. G.M. is a founding advisor and holds equity in Zephyr AI. F.X. and S.P. declare no competing interests.

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Xu, F., Saxena, D., Pushalkar, S. et al. Reply to: Revisiting the intrinsic mycobiome in pancreatic cancer. Nature 620, E7–E9 (2023). https://doi.org/10.1038/s41586-023-06293-0

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