Journal article
Human colitis-associated colorectal carcinoma progression is accompanied by dysbiosis with enriched pathobionts
Gut microbes, Vol.17(1), 2479774
12/2025
DOI: 10.1080/19490976.2025.2479774
PMCID: PMC11917176
PMID: 40094201
Abstract
Dysbiosis and pathobionts contribute to inflammation and the risk of colitis-associated carcinoma (CAC) in animal models, but their roles in humans with this uncommon disease are unknown. We identified microbiome differences in human CAC compared with longstanding inflammatory bowel disease (IBD) and sporadic colorectal carcinoma (CRC). Twenty-four CAC resections were matched with CRC and IBD controls. Methods included histopathology, 16S rDNA metagenomics, and pathobiont-specific qPCR. Beta diversity differed by diagnosis (PERMANOVA
= 0.007). The distinguishing taxa included
enriched in CRC, and
. enriched in IBD. The non-neoplastic mucosae presented distinct beta diversity (
= 0.005), but the CAC/CRC tumor microbiomes were similar (
= 0.7). Within metastases and margins, Enterobacteriaceae were enriched in CAC, and Bacteroidales in CRC. Pathobiont-specific qPCR confirmed a greater frequency of
and enterotoxigenic
in CAC than IBD. High alpha diversity was associated with active inflammation, advanced cancer stage, and shorter overall survival (log-rank
= 0.008). Mucosal microbiomes distinguish CAC from longstanding IBD, implicating pathobionts as markers for disease progression. Integrating our findings with prior animal model research, pathobionts promote carcinogenesis in IBD patients through genotoxicity and host cell signaling.
Details
- Title: Subtitle
- Human colitis-associated colorectal carcinoma progression is accompanied by dysbiosis with enriched pathobionts
- Creators
- Amr H Masaadeh - University of IowaMohamed Eletrebi - University of IowaBishal Parajuli - University of Iowa, PathologyNicola De Jager - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USADustin E Bosch - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Gut microbes, Vol.17(1), 2479774
- DOI
- 10.1080/19490976.2025.2479774
- PMID
- 40094201
- PMCID
- PMC11917176
- NLM abbreviation
- Gut Microbes
- ISSN
- 1949-0976
- eISSN
- 1949-0984
- Publisher
- TAYLOR & FRANCIS INC; PHILADELPHIA
- Grant note
- K08 AI159619 / NIAID NIH HHS
- Language
- English
- Date published
- 12/2025
- Academic Unit
- Pathology
- Record Identifier
- 9984802012802771
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