Primary tumor microbiomes predict distant metastasis of colorectal cancer

Bishal Parajuli; Vishal Midya; Ryan Kiddle; Nicola De Jager; Shoshannah Eggers; Daniel Spakowicz; Rebecca Hoyd; Bodour Salhia; Carlos H.F. Chan; Michelle L. Churchman; Robert J. Rounbehler; Song Yao; Melanie R. Rutkowski; Ahmad A. Tarhini; Dinesh Pal Mudaranthakam; Ashiq Masood; Therese J. Bocklage; Robert W. Lentz; Hassan Hatoum; Mmadili N. Ilozumba; Sheetal Hardikar; Cornelia M. Ulrich; June L. Round; Gregory Riedlinger; Craig D. Shriver; Dustin E. Bosch

doi:10.1038/s41698-025-01188-x

Primary tumor microbiomes predict distant metastasis of colorectal cancer

Bishal Parajuli, Vishal Midya, Ryan Kiddle, Nicola De Jager, Shoshannah Eggers, Daniel Spakowicz, Rebecca Hoyd, Bodour Salhia, Carlos H.F. Chan, Michelle L. Churchman, Robert J. Rounbehler, Song Yao, Melanie R. Rutkowski, Ahmad A. Tarhini, Dinesh Pal Mudaranthakam, Ashiq Masood, Therese J. Bocklage, Robert W. Lentz, Hassan Hatoum, Mmadili N. IlozumbaSheetal Hardikar, Cornelia M. Ulrich, June L. Round, Gregory Riedlinger, Craig D. Shriver, Dustin E. Bosch^*

^*Corresponding author for this work

Surgery

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Abstract

Metastasis causes most cancer-related deaths in colorectal carcinoma (CRC), and microbiome markers may have prognostic value. We hypothesized that primary tumor microbiomes predict distant metastases. We analyzed 5-year metastasis-free survival (MFS) in a retrospective cohort of 900 ORIEN CRC tumor microbiomes (RNAseq). ORIEN findings were validated on an independent cohort using 16S rDNA sequencing and pathobiont-specific qPCR. Microbiome alpha diversity was higher in primary tumors than metastases and positively correlated with metastasis risk. Microbiome beta diversity distinguished primary vs. metastasis and predicted 5-year MFS. High primary tumor abundance of B. fragilis and low F. nucleatum were associated with short MFS. Enterobacteriaceae, including E. coli, were enriched in metastases. qPCR identified increased enterotoxigenic B. fragilis and pks + E. coli detection in CRC metastasizers. Microbial co-occurrence analysis identified a 3-species clique that predicts metastasis (OR 1.9 [1.4–2.6]). Results suggest that primary tumor microbiomes and specific pathobionts are precision markers for metastasis risk.

Original language	English
Article number	405
Journal	npj Precision Oncology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41698-025-01188-x
State	Published - Dec 2025

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Parajuli, B., Midya, V., Kiddle, R., De Jager, N., Eggers, S., Spakowicz, D., Hoyd, R., Salhia, B., Chan, C. H. F., Churchman, M. L., Rounbehler, R. J., Yao, S., Rutkowski, M. R., Tarhini, A. A., Mudaranthakam, D. P., Masood, A., Bocklage, T. J., Lentz, R. W., Hatoum, H., ... Bosch, D. E. (2025). Primary tumor microbiomes predict distant metastasis of colorectal cancer. npj Precision Oncology, 9(1), Article 405. https://doi.org/10.1038/s41698-025-01188-x

@article{cc39f4efbb594da89cd04c04891ecc2f,

title = "Primary tumor microbiomes predict distant metastasis of colorectal cancer",

abstract = "Metastasis causes most cancer-related deaths in colorectal carcinoma (CRC), and microbiome markers may have prognostic value. We hypothesized that primary tumor microbiomes predict distant metastases. We analyzed 5-year metastasis-free survival (MFS) in a retrospective cohort of 900 ORIEN CRC tumor microbiomes (RNAseq). ORIEN findings were validated on an independent cohort using 16S rDNA sequencing and pathobiont-specific qPCR. Microbiome alpha diversity was higher in primary tumors than metastases and positively correlated with metastasis risk. Microbiome beta diversity distinguished primary vs. metastasis and predicted 5-year MFS. High primary tumor abundance of B. fragilis and low F. nucleatum were associated with short MFS. Enterobacteriaceae, including E. coli, were enriched in metastases. qPCR identified increased enterotoxigenic B. fragilis and pks + E. coli detection in CRC metastasizers. Microbial co-occurrence analysis identified a 3-species clique that predicts metastasis (OR 1.9 [1.4–2.6]). Results suggest that primary tumor microbiomes and specific pathobionts are precision markers for metastasis risk.",

author = "Bishal Parajuli and Vishal Midya and Ryan Kiddle and {De Jager}, Nicola and Shoshannah Eggers and Daniel Spakowicz and Rebecca Hoyd and Bodour Salhia and Chan, {Carlos H.F.} and Churchman, {Michelle L.} and Rounbehler, {Robert J.} and Song Yao and Rutkowski, {Melanie R.} and Tarhini, {Ahmad A.} and Mudaranthakam, {Dinesh Pal} and Ashiq Masood and Bocklage, {Therese J.} and Lentz, {Robert W.} and Hassan Hatoum and Ilozumba, {Mmadili N.} and Sheetal Hardikar and Ulrich, {Cornelia M.} and Round, {June L.} and Gregory Riedlinger and Shriver, {Craig D.} and Bosch, {Dustin E.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41698-025-01188-x",

language = "English",

volume = "9",

journal = "npj Precision Oncology",

issn = "2397-768X",

publisher = "Nature Research",

number = "1",

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Parajuli, B, Midya, V, Kiddle, R, De Jager, N, Eggers, S, Spakowicz, D, Hoyd, R, Salhia, B, Chan, CHF, Churchman, ML, Rounbehler, RJ, Yao, S, Rutkowski, MR, Tarhini, AA, Mudaranthakam, DP, Masood, A, Bocklage, TJ, Lentz, RW, Hatoum, H, Ilozumba, MN, Hardikar, S, Ulrich, CM, Round, JL, Riedlinger, G, Shriver, CD & Bosch, DE 2025, 'Primary tumor microbiomes predict distant metastasis of colorectal cancer', npj Precision Oncology, vol. 9, no. 1, 405. https://doi.org/10.1038/s41698-025-01188-x

TY - JOUR

T1 - Primary tumor microbiomes predict distant metastasis of colorectal cancer

AU - Parajuli, Bishal

AU - Midya, Vishal

AU - Kiddle, Ryan

AU - De Jager, Nicola

AU - Eggers, Shoshannah

AU - Spakowicz, Daniel

AU - Hoyd, Rebecca

AU - Salhia, Bodour

AU - Chan, Carlos H.F.

AU - Churchman, Michelle L.

AU - Rounbehler, Robert J.

AU - Yao, Song

AU - Rutkowski, Melanie R.

AU - Tarhini, Ahmad A.

AU - Mudaranthakam, Dinesh Pal

AU - Masood, Ashiq

AU - Bocklage, Therese J.

AU - Lentz, Robert W.

AU - Hatoum, Hassan

AU - Ilozumba, Mmadili N.

AU - Hardikar, Sheetal

AU - Ulrich, Cornelia M.

AU - Round, June L.

AU - Riedlinger, Gregory

AU - Shriver, Craig D.

AU - Bosch, Dustin E.

PY - 2025/12

Y1 - 2025/12

N2 - Metastasis causes most cancer-related deaths in colorectal carcinoma (CRC), and microbiome markers may have prognostic value. We hypothesized that primary tumor microbiomes predict distant metastases. We analyzed 5-year metastasis-free survival (MFS) in a retrospective cohort of 900 ORIEN CRC tumor microbiomes (RNAseq). ORIEN findings were validated on an independent cohort using 16S rDNA sequencing and pathobiont-specific qPCR. Microbiome alpha diversity was higher in primary tumors than metastases and positively correlated with metastasis risk. Microbiome beta diversity distinguished primary vs. metastasis and predicted 5-year MFS. High primary tumor abundance of B. fragilis and low F. nucleatum were associated with short MFS. Enterobacteriaceae, including E. coli, were enriched in metastases. qPCR identified increased enterotoxigenic B. fragilis and pks + E. coli detection in CRC metastasizers. Microbial co-occurrence analysis identified a 3-species clique that predicts metastasis (OR 1.9 [1.4–2.6]). Results suggest that primary tumor microbiomes and specific pathobionts are precision markers for metastasis risk.

AB - Metastasis causes most cancer-related deaths in colorectal carcinoma (CRC), and microbiome markers may have prognostic value. We hypothesized that primary tumor microbiomes predict distant metastases. We analyzed 5-year metastasis-free survival (MFS) in a retrospective cohort of 900 ORIEN CRC tumor microbiomes (RNAseq). ORIEN findings were validated on an independent cohort using 16S rDNA sequencing and pathobiont-specific qPCR. Microbiome alpha diversity was higher in primary tumors than metastases and positively correlated with metastasis risk. Microbiome beta diversity distinguished primary vs. metastasis and predicted 5-year MFS. High primary tumor abundance of B. fragilis and low F. nucleatum were associated with short MFS. Enterobacteriaceae, including E. coli, were enriched in metastases. qPCR identified increased enterotoxigenic B. fragilis and pks + E. coli detection in CRC metastasizers. Microbial co-occurrence analysis identified a 3-species clique that predicts metastasis (OR 1.9 [1.4–2.6]). Results suggest that primary tumor microbiomes and specific pathobionts are precision markers for metastasis risk.

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U2 - 10.1038/s41698-025-01188-x

DO - 10.1038/s41698-025-01188-x

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