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  • The Role of the Microbiome in Cancer: From Carcinogenesis to Therapeutic Response

  • Hanieh Safarzadeh,1 Mohsen Moghoofei,2,*
    1. Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
    2. Department of Virology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.


  • Introduction: The human microbiome has emerged as an important component of cancer biology, with increasing evidence suggesting its involvement in tumor initiation, progression, immune regulation, and therapeutic outcomes. Although only a limited number of microorganisms have been demonstrated to directly cause carcinogenesis, accumulating studies indicate that microbial dysbiosis and host–microbe interactions can influence cancer development through inflammatory signaling, metabolic alterations, genomic instability, and modulation of immune responses. The relationship between microbiota and cancer is complex and context-dependent, involving both tumor-promoting and potentially protective microbial functions. Recent advances have particularly highlighted the role of the gut microbiome and tumor-associated microbiota in regulating antitumor immunity and modifying responses to immune-based therapies.
  • Methods: A narrative review was conducted using published literature from PubMed and major biomedical databases. Studies addressing the relationship between microbiome composition, microbial metabolites, carcinogenesis, tumor microenvironment, immune regulation, and cancer therapy were evaluated. The literature search included the keywords microbiome, gut microbiota, tumor microbiome, cancer, carcinogenesis, dysbiosis, immune checkpoint inhibitors, microbial metabolites, and microbiome-based therapy. Relevant experimental studies, clinical investigations, and review articles were selected to summarize current mechanistic and translational evidence.
  • Results: Current evidence indicates that microbial alterations are associated with several stages of cancer development. In specific malignancies, particularly colorectal cancer, certain microorganisms such as Fusobacterium nucleatum, toxin-producing Bacteroides fragilis, and genotoxicity-associated bacterial strains have been linked to inflammatory responses, epithelial damage, and molecular pathways involved in tumorigenesis. However, the contribution of microbiota to cancer formation varies among tumor types, and direct causal relationships remain incompletely established. Beyond carcinogenesis, microbiota significantly influence the tumor microenvironment through microbial-associated molecular patterns, metabolites, and interactions with immune cells. Gut microorganisms can regulate innate and adaptive immune responses by affecting dendritic cells, macrophages, natural killer cells, and cytotoxic T lymphocytes. Increasing evidence demonstrates that gut microbiome composition is associated with variable responses to immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 therapies. Specific microbial profiles and metabolites may enhance antitumor immune activity, whereas dysbiotic states may contribute to immune suppression and treatment resistance. Recent studies have also identified the presence of tumor-associated microbiota within several solid tumors. These intratumoral microbial communities may influence tumor biology by modifying immune-cell infiltration, cytokine production, and immune checkpoint pathways. Nevertheless, this field remains emerging, and further studies are required to distinguish functional microbial populations from potential technical contamination and to clarify their clinical significance. Microbiome-based therapeutic approaches, including fecal microbiota transplantation, dietary modulation, probiotics, prebiotics, and engineered bacteria, are being investigated as strategies to improve cancer treatment outcomes. Early clinical studies suggest that microbiome modulation may enhance immunotherapy efficacy in selected patients; however, variability between individuals, methodological differences, safety concerns, and the lack of standardized microbial biomarkers remain important challenges.
  • Conclusion: The microbiome represents a dynamic biological factor that interacts with cancer development, tumor immunity, and therapeutic response. Current evidence supports an important association between microbial communities and cancer biology, particularly through inflammatory, metabolic, and immunological mechanisms. However, microbiome-based cancer applications remain an evolving field, and further longitudinal, multicenter, and multi-omics studies are necessary to establish causal mechanisms and develop clinically validated microbiome-guided strategies for cancer prevention, diagnosis, and treatment.
  • Keywords: Cancer; microbiome; gut microbiota; tumor microbiome; dysbiosis; carcinogenesis; tumor microenvironm

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