Microbial dysbiosis drives colorectal carcinogenesis via integrated inflammatory, metabolic, and biofilm pathways
8 affiliations
- 1Clinical Sciences Department, College of Medicine, University of Sharjah
- 2Research Institute of Medical and Health Sciences, University of Sharjah
- 3Center of Excellence for Precision Medicine, Research Institute of Medical and Health Sciences, University of Sharjah
- 4Oncology Unit, University Hospital Sharjah
- 5Pathology Department, Faculty of Medicine, Alexandria University
- 6ASPIRE Precision Medicine Research Institute Abu Dhabi, University of Sharjah
- 7BIMAI-Lab, Biomedically Informed Artificial Intelligence Laboratory, University of Sharjah
- 8Division of Surgery and Interventional Science, University College London
Abstract
Colorectal cancer (CRC) arises from a multifaceted interplay among the intestinal microbiota, chronic inflammation, and host genomic instability, with microbial dysbiosis serving as an active driver rather than a by-product of malignant transformation. Genotoxic Escherichia coli (colibactin-positive), enterotoxigenic Bacteroides fragilis , and Fusobacterium nucleatum contribute to distinct stages of CRC progression by engaging the DNA-damage response and activating β-catenin–dependent Wnt signaling and NF-κB/STAT3 transcriptional programs controlling pro-inflammatory ( IL-6, IL-8 ), pro-survival ( BCL-2, BCL-XL ), and proliferative ( MYC, CCND1 ) gene expression.. Here, we propose a tri-axial pathogenic framework in which (i) cyclic dinucleotide–mediated activation of the cGAS–STING pathway engages TBK1–IRF3 and NF-κB signaling, driving type I interferons ( IFN- β) and pro-inflammatory cytokines ( IL-6, TNF- α) that couple microbial genotoxic stress to innate inflammation; (ii) altered microbial metabolites, including indoles and bile acids, reprogram AhR and FXR/TGR5 signaling; and (iii) crypt-anchored biofilms spatially amplify IL-6 leading to activation of STAT3, epigenetic silencing of tumor suppressors, and immune evasion. This review critically synthesizes current evidence supporting these axes and maps them onto CRC molecular subsets and tumor location. Recognition of these integrated microbial-host circuits identifies mechanistically grounded candidates for biomarker development, microbiome-based diagnostics, and targeted interventions to restore microbial and immune equilibrium, thereby providing a refined framework for the molecular classification and precision management of CRC.
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BibTeX
@article{bachir2026microbial,
title = {{Microbial dysbiosis drives colorectal carcinogenesis via integrated inflammatory, metabolic, and biofilm pathways}},
author = {Asma Bachir and Alaa Muayad Altaie and Riyad Bendardaf and Iman M Talaat and Rifat Hamoudi},
journal = {Frontiers in Microbiology},
year = {2026},
month = jun,
doi = {10.3389/fmicb.2026.1795882},
url = {https://doi.org/10.3389/fmicb.2026.1795882},
note = {CC BY},
}
RIS
TY - JOUR
TI - Microbial dysbiosis drives colorectal carcinogenesis via integrated inflammatory, metabolic, and biofilm pathways
AU - Asma Bachir
AU - Alaa Muayad Altaie
AU - Riyad Bendardaf
AU - Iman M Talaat
AU - Rifat Hamoudi
PY - 2026
DA - 2026/06/02
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1795882
UR - https://doi.org/10.3389/fmicb.2026.1795882
AB - Colorectal cancer (CRC) arises from a multifaceted interplay among the intestinal microbiota, chronic inflammation, and host genomic instability, with microbial dysbiosis serving as an active driver rather than a by-product of malignant transformation. Genotoxic Escherichia coli (colibactin-positive), enterotoxigenic Bacteroides fragilis , and Fusobacterium nucleatum contribute to distinct stages of CRC progression by engaging the DNA-damage response and activating β-catenin–dependent Wnt signaling and NF-κB/STAT3 transcriptional programs controlling pro-inflammatory ( IL-6, IL-8 ), pro-survival ( BCL-2, BCL-XL ), and proliferative ( MYC, CCND1 ) gene expression.. Here, we propose a tri-axial pathogenic framework in which (i) cyclic dinucleotide–mediated activation of the cGAS–STING pathway engages TBK1–IRF3 and NF-κB signaling, driving type I interferons ( IFN- β) and pro-inflammatory cytokines ( IL-6, TNF- α) that couple microbial genotoxic stress to innate inflammation; (ii) altered microbial metabolites, including indoles and bile acids, reprogram AhR and FXR/TGR5 signaling; and (iii) crypt-anchored biofilms spatially amplify IL-6 leading to activation of STAT3, epigenetic silencing of tumor suppressors, and immune evasion. This review critically synthesizes current evidence supporting these axes and maps them onto CRC molecular subsets and tumor location. Recognition of these integrated microbial-host circuits identifies mechanistically grounded candidates for biomarker development, microbiome-based diagnostics, and targeted interventions to restore microbial and immune equilibrium, thereby providing a refined framework for the molecular classification and precision management of CRC.
SN - 1664-302X
ER -