Microbiome Cancer Axis
Corresponding author: [email protected]
Abstract
The cancer–microbiome axis refers to the bidirectional interactions between resident and tumor-associated microbial communities and host tumor biology, encompassing mechanisms of oncogenesis, tumor progression, immune modulation, and therapeutic response. Microbial dysbiosis and intratumoral colonization influence genomic instability, inflammation, immune editing, metabolic reprogramming, and barrier integrity, thereby shaping tumor initiation, growth, and metastasis. The oncobiome—comprising bacteria, fungi, viruses, and their metabolites—modulates signalling pathways and the tumor microenvironment (TME), contributing to carcinogenesis and therapy outcomes. Recent advances in metagenomics, metabolomics, and single-cell profiling have identified microbial signatures predictive of cancer risk and therapeutic efficacy, underscoring their potential as diagnostic biomarkers and therapeutic targets. Microbiome-based interventions—including probiotics, prebiotics, engineered commensals, and faecal microbiota transplantation—are being explored to enhance responses to immunotherapy, chemotherapy, and radiotherapy. Key pathways involve modulation of innate and adaptive immunity, alteration of estrogen and metabolic signalling, production of genotoxins and pro-tumor metabolites, and microbial ligands that engage receptors such as AhR, PXR, FXR, and TGR5, thereby influencing proliferation, apoptosis, angiogenesis, and therapy responsiveness. Intratumoral microbes act as local modulators of the TME, while gut, oral, biliary, and vaginal communities exert systemic effects that reach tumors. Microbial signatures in tumor tissue and biofluids (fecal, urine, bile, vaginal) show promise for early detection, prognosis, and prediction of therapeutic responses, including checkpoint inhibitors and cell-based therapies. Despite these advances, challenges remain in establishing causality, addressing inter-individual variability, and translating microbiome research into precision oncology. This chapter highlights current knowledge, mechanistic pathways, and therapeutic opportunities within the cancer–microbiome axis, emphasizing its role as a critical determinant of cancer biology and a novel avenue for personalized medicine.
Author Affiliations
- 1 Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Lucknow-226028, India.