The Human Microbiome in Cancer: Roles in Onset, Progression, and Therapeutic Response

The Human Microbiome in Cancer: Roles in Onset, Progression, and Therapeutic Response
Mehrad Mohammadi,^1,* Parsa Ashjaei,²
1. Islamic Azad University,Tehran Medical Branch
2. Islamic Azad University,Tehran Medical Branch
Introduction: In recent years, the role of the human microbiome in the onset, progression, and treatment of cancer has gained growing interest in biomedical sciences. The human microbiome, a diverse ecosystem of microorganisms including bacteria, viruses, fungi, and archaea, resides in various body sites, such as the gut, oral cavity, skin, and lungs. Among these, the gut microbiota is especially influential due to its high density and metabolic activity. This microbial community plays a vital role in modulating immune responses, maintaining mucosal integrity, regulating inflammatory processes, and metabolizing dietary compounds. Disruptions in its composition or function, known as dysbiosis, have been associated with several chronic conditions, including inflammatory bowel disease, metabolic syndrome, and various types of cancer. Alterations in the gut microbiota can lead to chronic inflammation and generate carcinogenic compounds, both of which contribute to tumor initiation. Conversely, beneficial microbes and their metabolites, such as short-chain fatty acids (SCFAs), help suppress inflammation, regulate immune tolerance, and may even protect against neoplastic transformation. Understanding these dual roles is crucial for identifying how the microbiome may contribute to carcinogenesis and serve as a potential therapeutic target.
Methods: This structured summary is based on a synthesis of recent experimental and clinical literature examining the association between the microbiome and cancer biology. Studies include both observational and interventional research, utilizing tools such as 16S rRNA gene sequencing, whole metagenome shotgun sequencing, fecal microbiota transplantation (FMT), and germ-free animal models. These approaches have enabled a detailed analysis of microbial diversity, functional gene expression, and interaction between microbial communities and the tumor microenvironment.
Results: Findings across multiple studies demonstrate that specific microbial taxa are enriched or depleted in cancer patients. Chronic inflammation, fueled by microbial dysbiosis, is a known risk factor for cancer. Pathogenic bacteria like Helicobacter pylori and Escherichia coli (with colibactin-producing genes) can activate inflammatory cascades (e.g., NF-κB pathway), damage epithelial DNA, and facilitate malignant transformation. In contrast, commensal microbes produce metabolites such as butyrate and propionate, which can inhibit histone deacetylases (HDACs), modulate gene expression, and induce apoptosis in cancer cells. Moreover, the gut microbiome is emerging as a key modulator of cancer immunotherapy efficacy. Several studies have shown that certain bacterial species, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bifidobacterium longum, are associated with better clinical responses to immune checkpoint inhibitors (e.g., PD-1 and CTLA-4 blockade). FMT from responders to germ-free mice enhances antitumor immunity, while antibiotic exposure before or during immunotherapy is linked to poorer outcomes. The discovery of intratumoral microbiota has further expanded our understanding of host-microbe interactions in cancer. Contrary to earlier assumptions that internal tissues are sterile, tumor tissues from breast, pancreatic, and lung cancers have shown microbial signatures. In some cases, these microbes directly impact treatment efficacy, for example, by inactivating chemotherapy agents like gemcitabine in pancreatic cancer. Additionally, the oral microbiome has been implicated in gastrointestinal malignancies; species such as Fusobacterium nucleatum have been identified in both oral plaques and colorectal tumor tissues, where they may suppress local immune surveillance.
Conclusion: The accumulating evidence underscores the microbiome’s multifaceted role in cancer pathogenesis, progression, and therapy. As our understanding deepens, microbiome-targeted interventions, ranging from probiotics and prebiotics to personalized dietary plans and FMT, are gaining attention as adjunctive or even primary strategies in cancer prevention and treatment. Microbiome profiling may also serve as a predictive biomarker for therapy selection, guiding personalized medicine. Emerging technologies such as next-generation sequencing, metagenomics, and systems biology are accelerating the identification of microbial functions relevant to cancer. While challenges remain, such as the need for standardized protocols, longitudinal data, and clearer mechanistic insights, the integration of microbiome science into oncology holds transformative potential. Future research will benefit from interdisciplinary collaboration bridging microbiology, immunology, oncology, computational biology, and clinical sciences.
Keywords: 1. Human Microbiome 2. Cancer Immunotherapy 3. Microbial Dysbiosis 4. Short-Chain Fatty Acids