The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostrptococcus stomatis, Parvimonas micra and Hungatella hathewayi, were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

The authors have declared no competing interest.

The study was supported by the National Natural Science Foundation of China [82073159, 82002467], the Natural Science Foundation of Guangdong [2022A1515012296], Beijing Xisike Clinical Oncology Research Foundation [Y-tongshu2021/ms-0175], Guangdong Genomics Data Center [2021B1212100001].

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All patients were recruited from Sun Yat-sen University Cancer Center in Guangzhou in accordance with the study protocol approved by the Ethics Committee of Sun Yat-sen University Cancer Center (B2019-214-X02).

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