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INTERNATIONAL CONGRESS OF

CancerGenetics

• The gut microbiom and colorectal cancer: a new frontier in aging, inflammation and therapeutic responses

• Samila Farokhimanesh,^1,* Shakiba SharifzadehArdakani ,² Negar Norouzi,³ Mohaddeseh Mirzaie,⁴
  1. Department of Biotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran.
  2. Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
  3. Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
  4. Faculty of Engineering and Basic Sciences, Eslamshahr Branch, Islamic Azad University, Eslamshahr, Iran
  
  
  
• Introduction: The gut microbiome, a highly dynamic and diverse microbial ecosystem withnin the gastrointestinal tract, exerts critical control over host metabolism, immune regulation, and systemic health. Throughout the human lifespan, microbial diversity evolves—peaking in adulthood and declining with age. This age-related shift, termed dysbiosis, is closely associated with multiple chronic conditions, most notably colorectal cancer (CRC), type 2 diabetes, cognitive decline, and frailty. Dysbiosis involves depletion of beneficial bacteria and expansion of pro-inflammatory species, creating an environment of chronic low-grade inflammation and metabolic disturbance that fosters tumor initiation and progression. In contrast, individuals with exceptional longevity often maintain microbiota rich in short-chain fatty-acid-producing and anti-inflammatory taxa, suggesting that microbial composition directly influences aging trajectories and cancer susceptibility. Recent research highlights the gut microbiome not only as a contributor to oncogenesis but also as a modifiable determinant of cancer treatment efficacy, particularly in the context of immunotherapy. Specific microbial communities modulate host responses to immune-checkpoint inhibitors, chemotherapeutics, and radiotherapy. Consequently, strategies targeting the microbiota—such as dietary modification, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT)—are gaining traction as adjuncts to conventional therapies. Additionally, cutting-edge technologies including nanoparticle-based drug delivery and multi-omics profiling enable more precise re-engineering of gut flora and truly personalized interventions.
• Methods: This review integrates data from experimental models, clinical studies, and omics-based analyses to elucidate the link between gut microbiota, aging, and CRC. Key methodologies include 16S rRNA sequencing, whole-metagenome profiling, and metabolomics to assess microbial structure and function. Animal models—such as PIRC mice, azoxymethane-induced carcinogenesis models, and germ-free systems—were pivotal in demonstrating causality between microbiota alterations and tumor development. FMT experiments frequently tested whether transferring healthy or dysbiotic communities could influence cancer risk and immune activity. Clinical trials further evaluated the effectiveness of prebiotics like inulin, natural compounds such as pectin, and nanoparticle carriers in reshaping the microbiome for therapeutic benefit. Comparative analyses using LEfSe and Bray-Curtis indices revealed age-related microbial patterns and treatment-response profiles, while artificial-intelligence algorithms generated predictive models based on compositional data.
• Results: Findings consistently demonstrate that the gut microbiome plays a central role in colorectal and gastric carcinogenesis, biological aging, and therapy responsiveness. Helicobacter pylori infection was confirmed as a major driver of gastric cancer, and its eradication success was modulated by baseline microbial ecology. Microbiota-based classifiers achieved strong predictive power for CRC, with area-under-the-curve values reaching 0.83 in certain cohorts. Furthermore, dietary interventions—particularly plant-based and pesco-vegetarian diets—enhanced microbial diversity and reduced pro-inflammatory metabolites, thereby suppressing tumorigenesis and oxidative stress. Beneficial taxa such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and members of the Ruminococcaceae family were consistently linked with improved immune function, longer survival, and superior therapeutic outcomes. Building on these observations, advanced delivery systems that combine microbiome-targeted strategies with nanomedicine significantly improved tumor control and mitigated systemic inflammation. Notably, aging correlated with reduced microbial diversity and a shift toward inflammatory profiles, reaffirming the role of dysbiosis in both tumor promotion and immune senescence. Collectively, these insights position the microbiome not only as a diagnostic and therapeutic target but also as a key mediator of health span.
• Conclusion: The gut microbiome emerges as a foundational element in the prevention, development, and treatment of colorectal cancer while simultaneously influencing the pace and quality of aging. Age-associated dysbiosis fosters a tumor-permissive environment through immune dysfunction and metabolic imbalance. However, accumulating evidence supports the feasibility of reversing these changes through strategic microbiome modulation. Interventions such as dietary refinement, engineered probiotics, FMT, and precision-medicine platforms—including multi-omics and nanotechnology—hold promise for enhancing treatment outcomes and promoting healthy aging. As oncology advances toward more personalized paradigms, integrating microbiome analytics with host genetic and immune profiling will be essential. This evolving understanding of host–microbe interactions opens the door to innovative, individualized strategies for cancer prevention and care.
• Keywords: Gut microbiome, colorectal cancer, Aging