Year: 2026 | Month: March | Volume: 13 | Issue: 3 | Pages: 139-152
DOI: https://doi.org/10.52403/ijrr.20260317
The Role of the Gut Microbiome in Colorectal Cancer Development and Therapeutic Response
Kiren Mohammed Khalid Damodar1, Ahmed Hashim Azeez2
1Department of Medicine, Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Georgia.
2Department of Medicine, Faculty of Medicine, Tbilisi State Medical University, Georgia.
Corresponding Author: Kiren Mohammed Khalid Damodar
ABSTRACT
Colorectal cancer (CRC) is a leading global malignancy (≈1.92–2.2 million new cases per year). Most CRCs (~85%) are microsatellite-stable (MSS), exhibit low tumor mutational burden, and respond poorly to immune checkpoint inhibitors (ICIs). Growing evidence links gut microbial dysbiosis to CRC pathogenesis, with oncogenic species (e.g. Fusobacterium nucleatum, pks+ E. coli, enterotoxigenic Bacteroides fragilis) promoting DNA damage, barrier disruption, chronic inflammation, and immune evasion. Conversely, depletion of beneficial commensals, including short-chain fatty acid (SCFA) producers such as Faecalibacterium and Akkermansia, reduces anti-inflammatory metabolite availability. These microbiota-driven processes intersect with oncogenic pathways, notably NF-κB/STAT3 and Wnt/β-catenin signaling. Distinct microbiome profiles are observed between MSI-High (dMMR) and MSS tumors, with dMMR tumors enriched in Fusobacterium, Akkermansia, and SCFA-producers, while MSS tumors show increased Proteobacteria (e.g. Serratia). The gut microbiota also modulates therapeutic response: certain commensals enhance anti-PD-1/CTLA-4 efficacy, whereas antibiotic-induced dysbiosis impairs ICI responses. Specific microbes can either sensitize or confer resistance to PD-1 blockade. Emerging strategies including fecal microbiota transplantation, probiotics, and dietary modulation aim to improve immunotherapy outcomes. Microbial biomarkers show diagnostic and prognostic potential in CRC.
Keywords: colorectal cancer; gut microbiome; microsatellite instability; immunotherapy; fecal microbiota transplantation; probiotics; biomarkers; inflammation.
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