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INTERNATIONAL CONGRESS OF

CancerGenetics

• The Gut Microbiome's Role in Colorectal Cancer Prognosis and Immunotherapy Response

• Mohamad Hossein Ramezani,^1,* Hafez Mozayyan Esfahani,²
  1. Department of Microbiology, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani University, Isfahan, Iran.
  2. Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
  
  
  
• Introduction: Colorectal cancer (CRC) is a major global health concern, ranking as the third most common cancer and a leading cause of cancer-related deaths [1]. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1, has transformed CRC treatment, especially for patients with microsatellite instability-high (MSI-H) tumors. However, response rates vary, prompting research into factors influencing efficacy. The gut microbiome, a diverse community of microorganisms in your digestive tract, plays a key role in how colorectal cancer (CRC) progresses and responds to immunotherapy, a treatment that boosts your immune system to fight cancer [2]. Certain bacteria can enhance or hinder the effectiveness of drugs like anti-PD-1, which help your immune system target cancer cells [3, 4]. This review explores how these microbes affect CRC treatment and what this means for future therapies.
• Methods: We searched scientific databases for studies from 2015 to 2025, focusing on how the gut microbiome influences CRC and immunotherapy. Only peer-reviewed studies in English were included, ensuring reliable and relevant information. The search targeted studies on microbial composition, mechanisms of immune modulation, and clinical interventions, using keywords like "gut microbiome," "colorectal cancer," and "immunotherapy."
• Results: Some bacteria, like Akkermansia muciniphila and Bifidobacterium, improve immunotherapy by boosting immune cell activity, enhancing anti-PD-1 efficacy via T-cell activation [5, 8]. Others, like Fusobacterium nucleatum, may worsen outcomes by suppressing immunity, contributing to poorer prognosis and resistance to ICIs, though its role is complex and debated [6]. High microbial diversity is associated with better immunotherapy responses [7]. Short-chain fatty acids (SCFAs) like butyrate boost immunity but can limit CTLA-4 blockade efficacy [9, 10]. Clinical trials show that transferring gut microbes from patients who respond well to immunotherapy can help others, with some achieving cancer-free status [17]. Dietary supplements like pectin show promise in enhancing treatment in preclinical models [14]. Probiotics such as Lactobacillus rhamnosus enhance PD-1 immunotherapy via the cGAS-STING pathway [15]. Mathematical modeling integrates microbial abundance and host immune status to predict immunotherapy responses [16]. Short-chain fatty acids (SCFAs) and their receptors play a role in gut inflammation and colon cancer [12]. Gut microbiota interactions with antitumor immunity are critical for CRC outcomes [13].
• Conclusion: The gut microbiome holds great potential for improving CRC treatment, but differences in microbial profiles among individuals make it challenging to apply universally. It seems likely that microbiome-based interventions, such as fecal microbiota transplantation (FMT) and prebiotics like pectin, improve immunotherapy responses, but variability among patients poses challenges. Future research could lead to personalized treatments that use your unique microbiome to fight cancer more effectively, integrating novel approaches like mathematical modeling.
• Keywords: Gut microbiome, colorectal cancer, immunotherapy, immune checkpoint inhibitors, probiotics.