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

## TL;DR

This study reviews current research on gut microbiome differences in early-onset colorectal cancer patients, highlighting gaps in understanding and suggesting future research directions.

## Contribution

The study systematically maps and identifies methodological gaps in gut microbiome research specific to early-onset colorectal cancer.

## Key findings

- EoCRC patients show lower α diversity and higher abundance of specific bacteria like Flavonifractor plautii and Fusobacteria.
- Comparisons with late-onset CRC reveal distinct β diversity and bacterial abundance patterns in EoCRC.
- Only limited studies link gut microbiota to clinicopathological features, suggesting associations with tumor location and survival.

## Abstract

The incidence of early-onset colorectal cancer (EoCRC) is rising globally, yet the underlying causes of this increase remain poorly understood. Most cases of EoCRC are sporadic and associated with environmental exposures. Growing evidence suggests that the gut microbiome may play a critical role in colorectal carcinogenesis, including tumor initiation and progression. This has led to the hypothesis that gut dysbiosis could partially account for the rising incidence of EoCRC. However, the current literature on this topic remains limited. This study aims to systematically map and synthetize the existing evidence on the gut microbiome characterization in EoCRC, with a particular focus on the methodologies employed. By identifying existing knowledge gaps and methodological limitations, this review seeks to inform future research directions and clarify the role of the gut microbiome in EoCRC. Ultimately this may lead to the discovery of modifiable microbial targets, offering novel strategies for the prevention or adjunctive treatment of colorectal cancer and contributing to the reduction in disease burden.

Background/Objectives: 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. Methods: 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. Results: 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 Flavonifractor plautii, Akkermansia muciniphila, Bacteroides, and Fusobacteria. Comparisons with LoCRC showed that EoCRC had distinct β diversity and a higher abundance in Fusobacterium, Akkermansia, Bacteroides, and Actinomyces. Only three studies correlated the microbiota composition of EoCRC with clinicopathology features and suggested positive associations between Fusobacterium abundance, rectal tumors and lower survival and Akkermansia abundance with body mass index (BMI) ≥ 25 kg/m2, rectal EoCRC, and better survival. Conclusions: 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.