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Correspondence to Dr Yanlei Ma, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; [email protected]
WHAT IS ALREADY KNOWN ON THIS TOPIC
The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing.
Multiple studies have suggested a critical role for the gut microbiota and metabolites in the pathogenesis of CRC.
Characteristics of the microbiota, metabolites, microbial enzyme-involved interactions and diagnostic efficacy of these biomarkers in patients with EO-CRC have not been reported.
WHAT THIS STUDY ADDS
Reduced alpha-diversity and shifted stool microbiome and metabolome were apparent in both, late-onset CRC (LO-CRC) and EO-CRC.
Fusobacterium nucleatum enrichment and short-chain fatty acid depletion characterise LO-CRC, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production.
Enriched Flavonifractor plauti and elevated red meat intake-related species, choline metabolites, KEGG orthology (KO) pldB and cbh gene axis may be potential tumour stimulators in EO-CRC.
The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from the control.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Altered microbiome–metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC.
The potential of gut microbiota-derived biomarkers to be used as promising non-invasive tools for the accurate detection and distinction of individuals with EO-CRC.
Introduction
The increase in early-onset cancers in various organs has become a global concern, particularly early-onset colorectal cancer (EO-CRC) diagnosed before the age of 50, whose incidence is steadily rising in many parts of the world.1–3 There are several possible reasons for this alarming finding. Younger patients are not covered by routine CRC screening owing to the traditional recommendation that CRC screening start at the age of 50. Patients with EO-CRC have also shown adverse pathological features and more advanced stages of CRC, and there remains a lack of diagnostic and therapeutic protocols dedicated to sporadic CRC in young individuals.4 Although multiple factors may be involved, including genetics and the environment, it is unclear whether there are unique molecular signatures and multiomics profiles underlying this cohort of patients with EO-CRC.
The link between CRC, the gut microbiota and its metabolites has been supported by several studies.5 6 Interestingly, the impact of gut microbiota on health seems to be important in...