The microbiome-metabolome axis in colorectal cancer therapy resistance: mechanisms, mediators, and therapeutic opportunities
6 affiliations
- 1Department of Medicine, Ziauddin Medical College
- 2Department of Medicine, Dow University of Health Sciences
- 3Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University
- 4Verspeeten Family Cancer Centre, London Health Sciences Centre
- 5Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University
- 6Cancer Research Institute, Office of Research and Sponsored Programs, Abu Dhabi University
Abstract
Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with therapeutic resistance representing a significant barrier to improved patient outcomes. Although tumor-intrinsic genetic alterations are important determinants of treatment resistance, emerging evidence suggests that the gut microbiome and its metabolites may also influence responses to chemotherapy, targeted therapy, and immunotherapy. The microbiome and metabolome function as an interconnected axis that can influence host immunity, microbial drug metabolism, epithelial homeostasis, and tumor-associated signaling pathways, thereby contributing to variation in therapeutic response. Despite advances in microbiome research, the mechanisms by which the microbiome-metabolome axis promotes therapy resistance are not fully elucidated, and clinical translation is limited by the absence of standardized biomarkers and validated therapeutic strategies. This review synthesizes current evidence on the molecular mechanisms through which the microbiome-metabolome axis contributes to CRC therapy resistance, with emphasis on microbial dysbiosis, bacterial metabolites, and host-microbial interactions in modulating treatment efficacy. Emerging microbiome-directed therapeutic approaches, including fecal microbiota transplantation, defined microbial consortia, dietary interventions, microbial metabolites, and engineered microbial therapies, are examined, along with the methodological and translational challenges that must be addressed before their integration into routine clinical practice.
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BibTeX
@article{khan2026microbiomemetabolome,
title = {{The microbiome-metabolome axis in colorectal cancer therapy resistance: mechanisms, mediators, and therapeutic opportunities}},
author = {Anoud Khan and Aryan Tareen and Anusha Abdul Muqeet Farid and Ahrar Amin and Hamza Nawaz Khan and Danial Khan Hadi and Saqib Raza Khan and Afsheen Raza},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1985675},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1985675/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The microbiome-metabolome axis in colorectal cancer therapy resistance: mechanisms, mediators, and therapeutic opportunities
AU - Anoud Khan
AU - Aryan Tareen
AU - Anusha Abdul Muqeet Farid
AU - Ahrar Amin
AU - Hamza Nawaz Khan
AU - Danial Khan Hadi
AU - Saqib Raza Khan
AU - Afsheen Raza
PY - 2026
DA - 2026/10/28
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1985675
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1985675/full
AB - Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with therapeutic resistance representing a significant barrier to improved patient outcomes. Although tumor-intrinsic genetic alterations are important determinants of treatment resistance, emerging evidence suggests that the gut microbiome and its metabolites may also influence responses to chemotherapy, targeted therapy, and immunotherapy. The microbiome and metabolome function as an interconnected axis that can influence host immunity, microbial drug metabolism, epithelial homeostasis, and tumor-associated signaling pathways, thereby contributing to variation in therapeutic response. Despite advances in microbiome research, the mechanisms by which the microbiome-metabolome axis promotes therapy resistance are not fully elucidated, and clinical translation is limited by the absence of standardized biomarkers and validated therapeutic strategies. This review synthesizes current evidence on the molecular mechanisms through which the microbiome-metabolome axis contributes to CRC therapy resistance, with emphasis on microbial dysbiosis, bacterial metabolites, and host-microbial interactions in modulating treatment efficacy. Emerging microbiome-directed therapeutic approaches, including fecal microbiota transplantation, defined microbial consortia, dietary interventions, microbial metabolites, and engineered microbial therapies, are examined, along with the methodological and translational challenges that must be addressed before their integration into routine clinical practice.
SN - 2234-943X
ER -