Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients
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Abstract
Background: Colibactin, a genotoxin produced by polyketide synthase harboring ( pks + ) bacteria, induces double-strand breaks and chromosome aberrations. Consequently, enrichment of pks + Escherichia coli in colorectal cancer and polyposis suggests a possible carcinogenic effect in the large intestine. Additionally, specific colibactin-associated mutational signatures; SBS88 and ID18 in the Catalogue of Somatic Mutations in Cancer database, are detected in colorectal carcinomas. Previous research showed that a recurrent APC splice variant perfectly fits SBS88. Methods: In this study, we explore the presence of colibactin-associated signatures and fecal pks in an unexplained polyposis cohort. Somatic targeted Next-Generation Sequencing (NGS) was performed for 379 patients. Additionally, for a subset of 29 patients, metagenomics was performed on feces and mutational signature analyses using Whole-Genome Sequencing (WGS) on Formalin-Fixed Paraffin Embedded (FFPE) colorectal tissue blocks. Results: NGS showed somatic APC variants fitting SBS88 or ID18 in at least one colorectal adenoma or carcinoma in 29% of patients. Fecal metagenomic analyses revealed enriched presence of pks genes in patients with somatic variants fitting colibactin-associated signatures compared to patients without variants fitting colibactin-associated signatures. Also, mutational signature analyses showed enrichment of SBS88 and ID18 in patients with variants fitting these signatures in NGS compared to patients without. Conclusions: These findings further support colibactins ability to mutagenize colorectal mucosa and contribute to the development of colorectal adenomas and carcinomas explaining a relevant part of patients with unexplained polyposis.
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E. coli Nissle 1917 synthesizes and releases colibactin, a mutagenic substance that promotes colorectal polyposis and cancer and reduces cancer response to irinotecan.
“having the capability of synthetizing and releasing colibactin, a mutagenic substance described to promote colorectal polyposis and cancer, and reducing cancer response to irinotecan [26, 34–39].”
From Selection, Comparative Genomics, and Potential Probiotic Features of Escherichia coli 5C, a pks-Negative Strain Isolated from Healthy Infant Donor Feces (2026) · cites this paper as [38]
The Background (page not provided) says pks-harboring E. coli can produce the genotoxin colibactin, and the Discussion links colibactin-associated signatures to colorectal lesions. The copy does not identify E. coli Nissle 1917, establish that it releases colibactin, or address response to irinotecan. (LLM, conf=0.88)
Experimental — accuracy not yet measuredE. coli Nissle 1917 is pks-positive.
“the most widely used E. coli-based probiotic, known as E. coli Nissle 1917 (DSM 6601), is pks-positive.”
From Selection, Comparative Genomics, and Potential Probiotic Features of Escherichia coli 5C, a pks-Negative Strain Isolated from Healthy Infant Donor Feces (2026) · cites this paper as [38]
The Background discusses pks-bearing E. coli generally, and the Results report pks genes in patient fecal samples. Neither identifies E. coli Nissle 1917 as pks-positive. Searches for “Nissle 1917” and “DSM 6601” found no passage addressing that strain. (LLM, conf=0.75)
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- Authors
- Terlouw, D., Boot, A., Ducarmon, Q. R., Nooij, S., Suerink, M., van Leerdam, M. E., van Egmond, D., Tops, C. M., Zwittink, R. D., Ruano, D., Langers, A. M. J., Nielsen, M., van Wezel, T., & Morreau, H.
- Affiliations
- Leiden University Medical Center (NL)
- National University of Singapore (SG)
- Corresponding author
- Morreau, Hans
- ORCID
- Venue
- BMC Cancer
- Published
- 2024-01-18
- Volume
- 24
- Issue
- 1
- Pages
- 104-104
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC10797792
- OpenAlex
- W4390974659
- Cited by
- 15
- References
- 30
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 2
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Cancer (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- KWF Kankerbestrijding (11292)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- colibactin, mutational signatures, colorectal polyposis, colorectal adenoma, colorectal cancer, PKS genes, fecal microbiota, Escherichia coli, somatic mutations, colorectal carcinogenesis
- MeSH terms
- Adenoma, Carcinoma, Escherichia coli, Humans, Mutation, Peptides, Colorectal Neoplasms, Polyketides
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