Hologenomic analysis of rectal mucus sampling for detection of adenomatous polyps and colorectal cancer

Andrew J. Tock, Kamrun S. Patel, Emma Morales-Walker, Linglan Zhang, Chris Orthodoxou, Alasdair D. MacRitchie, Stephen Njoroge, Oladapo E. Olaniru, Guy Mozolowski, Inês Mendes, Dave J. Baker, Malvin Siew, Hannah N. Humphrey, Eleanor T. Walker-Davies, Frank McDermott, Sue Spencer, Susan Bird, Katerina-Vanessa Savva, Christopher Cunningham, Hannah Rottenburg, Heena Sisodia, Nick J. Battersby, Gareth A. R. Jones, Jon Lacy-Colson, Alice E. Baggaley, Christopher J. Peters, Andrew Dodd, Kiran Kang, Chris Hamon, Ana Crespillo-Casado, Erica Law, Megan Sands, Hugo Lywood, Andrew J. Page, Ian Daniels and Daniel Wise ()
Additional contact information
Andrew J. Tock: Granta Park, Origin Sciences
Kamrun S. Patel: Granta Park, Origin Sciences
Emma Morales-Walker: Granta Park, Origin Sciences
Linglan Zhang: Granta Park, Origin Sciences
Chris Orthodoxou: Granta Park, Origin Sciences
Alasdair D. MacRitchie: Granta Park, Origin Sciences
Stephen Njoroge: Granta Park, Origin Sciences
Oladapo E. Olaniru: Granta Park, Origin Sciences
Guy Mozolowski: Granta Park, Origin Sciences
Inês Mendes: Suite 400, Theiagen Genomics
Dave J. Baker: Norwich, Quadram Institute Bioscience, Research Park
Malvin Siew: Granta Park, Origin Sciences
Hannah N. Humphrey: Exeter, Royal Devon University Healthcare NHS Foundation Trust
Eleanor T. Walker-Davies: Exeter, Royal Devon University Healthcare NHS Foundation Trust
Frank McDermott: Exeter, Royal Devon University Healthcare NHS Foundation Trust
Sue Spencer: Granta Park, Origin Sciences
Susan Bird: Headington, John Radcliffe Hospital, Headley Way
Katerina-Vanessa Savva: Imperial College London, Department of Surgery and Cancer
Christopher Cunningham: Headington, John Radcliffe Hospital, Headley Way
Hannah Rottenburg: Exeter, Royal Devon University Healthcare NHS Foundation Trust
Heena Sisodia: Truro, Royal Cornwall Hospital, Treliske
Nick J. Battersby: Truro, Royal Cornwall Hospital, Treliske
Gareth A. R. Jones: Shrewsbury and Telford NHS Trust
Jon Lacy-Colson: Shrewsbury and Telford NHS Trust
Alice E. Baggaley: Imperial College London, Department of Surgery and Cancer
Christopher J. Peters: Imperial College London, Department of Surgery and Cancer
Andrew Dodd: Granta Park, Origin Sciences
Kiran Kang: Granta Park, Origin Sciences
Chris Hamon: Granta Park, Origin Sciences
Ana Crespillo-Casado: Granta Park, Origin Sciences
Erica Law: Granta Park, Origin Sciences
Megan Sands: Granta Park, Origin Sciences
Hugo Lywood: Granta Park, Origin Sciences
Andrew J. Page: Granta Park, Origin Sciences
Ian Daniels: Granta Park, Origin Sciences
Daniel Wise: Granta Park, Origin Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-24

Abstract: Abstract Colorectal cancer (CRC) is the fourth most common cancer and the third leading cause of cancer-related mortality worldwide, with incidence rising among younger populations. The significant clinical and economic burden highlights the need for minimally invasive technologies capable of detecting pre-malignant and early-stage disease. Although liquid biopsy approaches have advanced, they have not achieved sufficient performance for clinical adoption when compared with colonoscopy, the current diagnostic gold standard. CRC is a mucosal pathology, yet current diagnostic methods have not leveraged mucosal biology. Here we demonstrate the clinical utility of rectal mucus specimens, collected using a minimally invasive device in an outpatient setting, without bowel preparation. Through a hologenomic approach integrating host and microbial genomics, we identify genetic and epigenetic aberrations and perturbations in microbial communities that drive the detection of adenomatous polyps and CRC in rectal mucus. Hologenomic integration enables superior stratification of CRC by disease site and stage compared with single-omics methods. In summary, we demonstrate the clinical utility of rectal mucus sampling combined with hologenomic analysis as a translatable prospective tool for diagnostic application.

Date: 2025
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DOI: 10.1038/s41467-025-66006-1

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