The Knowledge Gap in Gut Microbiome Characterization in Early-Onset Colorectal Cancer Patients: A Systematic Scoping Review.

Abstract

<h4>Background/objectives</h4>Over the past two decades, the incidence of early-onset colorectal cancer (EoCRC) has been increasing, although its underlying causes remain unclear. Gut microbiome is known to play a role in carcinogenesis of colorectal cancer. This scoping review aims to systematically map and synthetize current evidence on gut microbiome characterization in EoCRC (vs. late-onset colorectal cancer (LoCRC) and healthy individuals), describe the methodology used, and identify knowledge gaps to inform and guide future research.<h4>Methods</h4>This systematic scoping review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews. Searches were conducted in PubMed, Web of Science, and Scopus between January and February 2025. Two reviewers independently screened and selected the studies. One reviewer extracted the relevant information, using an adapted version of the JBI template.<h4>Results</h4>Seven studies met eligibility criteria. Compared to healthy young adults, EoCRC patients had a predominance of lower α diversity, different β diversity, and greater abundance of <i>Flavonifractor plautii</i>, <i>Akkermansia muciniphila</i>, <i>Bacteroides</i>, and <i>Fusobacteria.</i> Comparisons with LoCRC showed that EoCRC had distinct β diversity and a higher abundance in <i>Fusobacterium</i>, <i>Akkermansia</i>, <i>Bacteroides</i>, and <i>Actinomyces</i>. Only three studies correlated the microbiota composition of EoCRC with clinicopathology features and suggested positive associations between <i>Fusobacterium</i> abundance, rectal tumors and lower survival and <i>Akkermansia</i> abundance with body mass index (BMI) ≥ 25 kg/m², rectal EoCRC, and better survival.<h4>Conclusions</h4>There is a lack of large, methodologically robust studies linking gut microbiota with clinicopathological, lifestyle, and tumor molecular features in EoCRC. Our review highlights critical knowledge gaps, the need for standardized methodologies, and key areas for future investigation.