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INTERNATIONAL CONGRESS OF

CancerGenetics

• The Oncobiome in Precision Cancer Care: Microbiome-Guided Diet and Personalized Therapeutics

• Eman Koosehlar,¹ Mahdis Zolfaghar,² Maryam Khalifeh Soltani,³ Elena Valijanian,^4,*
  1. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Novazinogene Company, Tehran, Iran
  2. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Novazinogene Company, Tehran, Iran
  3. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Novazinogene Company, Tehran, Iran
  
  
  
• Introduction: The oncobiome, comprising microorganisms and their functional activity within the host and tumor microenvironment, is increasingly recognized as a critical factor in cancer risk, progression, and therapy response. Microbial dysbiosis can promote oncogenesis through bile acid dysregulation, chronic inflammation, and immune suppression, while beneficial taxa such as Faecalibacterium prausnitzii and Akkermansia muciniphila enhance anti-tumor immunity. Clinical evidence shows that gut microbiome composition and metabolites influence the efficacy of immune checkpoint inhibitors (ICIs), with antibiotic exposure reducing therapeutic benefit. These findings have driven interest in microbiota-targeted interventions—including probiotics, next-generation probiotics, and fecal microbiota transplantation (FMT)—which are showing potential in restoring immunotherapy responsiveness and mitigating treatment-related toxicities.
• Methods: Diet is a major determinant of microbiome composition and function, positioning microbiome–diet interactions as central modulators of cancer prevention and therapy. Fiber- and polyphenol-rich diets promote short-chain fatty acid (SCFA) production with anti-inflammatory and anti-carcinogenic properties, while Western-style diets favor metabolites that support tumorigenesis. Precision nutrition approaches, tailored to individual microbiome and metabolic profiles, are emerging as adjuncts to improve immunotherapy outcomes and reduce immune-related adverse effects. Nutrients such as omega-3 fatty acids, polyphenols, and amino acids like tryptophan regulate inflammation, antigen presentation, and T-cell activation, thereby synergizing with ICIs and CAR-T cell therapies. Early-phase clinical studies report that patients receiving dietary interventions aligned with their microbiome and metabolic signatures exhibit improved therapeutic responses and reduced toxicities. Combined strategies that integrate dietary modulation with microbiota-directed interventions, including probiotics, prebiotics, and FMT, show promise in enhancing therapeutic efficacy by supporting barrier integrity and immune balance.
• Results: FMT has emerged as a therapeutic strategy for restoring gut microbial balance in dysbiosis by transferring minimally processed stool from healthy donors—or from a patient’s own previously collected sample—via oral capsules or intestinal infusion. Initially established as an effective treatment for recurrent Clostridioides difficile infection (CDI) with success rates near 90%, FMT is now being investigated in oncology. Studies in melanoma, lung cancer, and hematologic malignancies have shown restored ICI responsiveness, improved microbial balance, and even successful decolonization of resistant bacteria. The importance of gut microbiome composition in shaping cancer therapy response is underscored by findings linking antibiotic exposure to reduced survival in ICI-treated patients and by preclinical models showing that Akkermansia muciniphila enhances antitumor immunity. Alongside FMT, probiotics have gained attention as live microorganisms conferring health benefits through mechanisms such as competitive inhibition of pathogens, production of bioactive metabolites, and immune modulation. Probiotics like Lactobacillus and Bifidobacterium demonstrate anticancer effects by detoxifying carcinogens, stimulating NK and T-cell responses, and reducing inflammatory pathways, while next-generation probiotics (NGPs)—including SCFA-producing taxa such as Faecalibacterium prausnitzii and Akkermansia muciniphila—are being investigated for more targeted anticancer effects and synergy with ICIs. Collectively, these findings highlight the therapeutic potential of microbiome-based interventions in oncology, though some challenges remain.
• Conclusion: Artificial intelligence (AI) is emerging as a powerful tool for integrating multi-omics, microbiome, dietary, and lifestyle data to advance personalized nutrition and cancer interventions. The gut microbiome shows high inter-individual heterogeneity, shaped by genetics, diet, medication, environment, and lifestyle, making integrative approaches essential for precision therapy. Cancer itself is highly complex, involving tumor genetics, the microenvironment, immune infiltration, and metabolic and epigenetic alterations. AI can synthesize diverse datasets—including metagenomics, metatranscriptomics, cancer genomics, immunological profiles, and clinical history—alongside diet and lifestyle factors to inform individualized therapies such as dietary or probiotic-based interventions. Nutritional studies illustrate both benefits and risks: high-fiber diets enrich butyrate-producing bacteria that enhance immunotherapy, while fat-rich Western diets increase pro-inflammatory, genotoxin-producing microbes that impair efficacy. To address such variability, AI-driven models are being developed, ranging from ML and DL frameworks (e.g., phyLoSTM, MetaNN, ML4Microbiome, MVIB, DeepMicro) to multimodal integrative tools (e.g., PROTEIN, MicrobiomeKG, McMLP, mNODE) and simulation-based approaches such as MCMM and BN-BacArena, which predict metabolic responses to diet or engineer microbiome interactions for therapeutic benefit. Despite these advances, challenges remain, including limited high-quality datasets, technical heterogeneity across sequencing and analysis platforms, the need for real-time diet and lifestyle monitoring, clinical validation of predictive models, and concerns over data privacy and sharing. Overcoming these barriers will be critical for developing robust AI platforms capable of dynamically simulating microbiome–host–diet interactions and guiding optimized, personalized cancer therapies.
• Keywords: Oncobiome, Gut microbiota, Personalized diet, FMT