INTERNATIONAL CONGRESS OF
CancerGenetics
The Role of Gut Microbiome in Colorectal Cancer
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Mitra Nicksirat ,1,*
1. Lorestan University of Medical Sciences, Khorramabad, Iran
- Introduction: Colorectal cancer (CRC) is one of the most common malignancies worldwide, posing a substantial public health challenge. While traditional risk factors such as genetics, lifestyle, and diet are well-established, emerging research has underscored the profound influence of the gut microbiome on CRC development and progression. The human gut harbors trillions of microorganisms, collectively known as the gut microbiota, which play crucial roles in host metabolism, immune system modulation, and protection against pathogens. An imbalance in this complex ecosystem, termed dysbiosis, has been increasingly linked to various chronic diseases, including cancer. The conceptual framework for gut microbiome involvement in CRC can be summarized as follows:Dysbiosis→ Inflammation/Carcinogenic Metabolites → Genetic Changes → CRC This pathway illustrates how microbial imbalance leads to chronic inflammation and production of harmful metabolites, which subsequently induce genetic alterations in colonic epithelial cells, ultimately resulting in colorectal cancer development. Recent advancements in metagenomic sequencing and functional analyses have enabled a deeper understanding of the specific microbial species and their metabolic pathways involved in CRC. This review aims to consolidate the latest findings from original research articles to provide a comprehensive overview of the multifaceted role of the gut microbiome in colorectal cancer. Specifically, we will discuss how alterations in microbial composition, microbial metabolites, and host-microbe interactions contribute to CRC pathogenesis, and explore the implications for novel diagnostic and therapeutic strategies.
- Methods: To ensure a focused and relevant review, a systematic approach was employed for the selection of original research articles. The primary objective was to identify studies published within the last year that provide novel insights into the role of the gut microbiome in colorectal cancer. The search strategy involved using reputable scientific databases including PubMed, Scopus, Nature, ScienceDirect, and Frontiers. The search was conducted for articles published between August 2024 and August 2025. Key search terms and their combinations used were: "gut microbiome colorectal cancer original research", "colorectal cancer gut microbiota study", "colorectal cancer gut microbiome pathogenesis", "gut microbiota CRC biomarkers", and "gut microbiome colorectal cancer therapy". Initially, a broad search using these keywords yielded a substantial number of articles. After an initial screening based on titles and abstracts, articles that were not original research (e.g., reviews, editorials, commentaries), not directly related to the gut microbiome and colorectal cancer, or published outside the specified timeframe were excluded. Preference was given to articles that were peer-reviewed, highly cited, and offered mechanistic insights or large-scale analyses. From the remaining pool, five original research articles were ultimately selected based on their direct relevance to the topic, methodological rigor, and significant contributions to the understanding of gut microbiome-CRC interplay. The selection process prioritized studies that utilized advanced techniques such as whole-genome metagenomic sequencing, animal models with humanized microbiomes, and large patient cohorts. The selected articles are detailed in the following sections, with a summary of their key findings and implications.
- Results: Analysis of the five selected original research studies highlights a consistent and multifaceted involvement of the gut microbiome in the initiation, progression, and potential therapeutic modulation of colorectal cancer (CRC). Despite differences in populations and methodologies, several converging findings emerged. 1. Consistent Dysbiosis Across the CRC Spectrum Meta-analyses of large metagenomic datasets revealed reproducible patterns of microbial imbalance spanning healthy individuals, patients with adenomas, and those with established CRC. Piccinno et al., using data from over 9,000 stool metagenomes across 20 cohorts, identified strain-level microbial biomarkers consistently associated with each stage of disease. These findings underscore the potential of stool-based microbial profiling as a non-invasive risk stratification and screening tool. 2. High-Risk Microbial Profiles Wang et al. demonstrated that first-degree relatives of CRC patients exhibit significant microbial alterations, with elevated levels of Fusobacterium and Bacteroides and decreased levels of beneficial bacteria such as Coprococcus and Roseburia. Although the Disease Probability (POD) model developed in their study did not achieve statistical significance in validation, the data highlight the potential role of microbiome shifts in early risk prediction. Similarly, Deng et al. observed that patients with colorectal polyps showed increased abundance of Bacteroides, Fusobacteria, and Proteobacteria alongside reduced levels of Bifidobacterium. Notably, Escherichia and Shigella were proposed as promising early biomarkers for detecting precancerous lesions. 3. Functional and Metabolic Roles Functional analyses demonstrated that the metabolic activities of the gut microbiome can directly influence tumor biology. In a humanized mouse model, Tsenkova et al. revealed that a ketogenic diet (KD) promotes the growth of stearic acid–producing bacteria, leading to higher levels of intraluminal stearate. This metabolite was shown to induce apoptosis in tumor cells and reduce pro-inflammatory Th17 cells, highlighting the therapeutic potential of diet-driven microbial modulation. 4. Novel Microbial Drivers and Genetic Insights Through ultra-deep metagenomic sequencing of over 3,000 samples, Minot et al. identified previously unrecognized bacteria and gene-level signatures linked to CRC. Experimental validation confirmed that several of these taxa could drive early precancerous changes, including gene expression shifts in colonic fibroblasts. This work broadens the understanding of CRC-associated microbes beyond the well-known Fusobacterium nucleatum. 5. Methodological Robustness and Limitations The reproducibility of key microbial signatures across independent cohorts strengthens their clinical relevance. However, variations in sequencing platforms, sample processing, and bioinformatic workflows remain a major limitation, indicating the need for standardized pipelines to improve cross-study comparability.
- Conclusion: The gut microbiome is an undeniable and influential player in the complex etiology and progression of colorectal cancer. The collective evidence from recent original research, including the studies reviewed herein, paints a clear picture of its multifaceted involvement. From shaping the early stages of polyp formation to influencing tumor growth and potentially modulating therapeutic responses, the gut microbiota offers a rich landscape for novel scientific inquiry and clinical translation. Key takeaways from this review include the consistent identification of specific microbial dysbiosis patterns in CRC patients and their relatives, the discovery of novel bacterial species and their gene-level contributions to precancerous changes, and the elucidation of how microbial metabolites, such as stearic acid, can exert direct anti- cancer effects. The advancements in large-scale metagenomic analyses have providedrobust, reproducible biomarkers, paving the way for non-invasive screening and personalized risk assessment.
- Keywords: Gut Microbiome, Colorectal Cancer, Microbiota, Dysbiosis, Probiotics
