Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer
Abstract
Objective: The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing. Here, we aimed to characterise the interactions between gut microbiome, metabolites and microbial enzymes in EO-CRC patients and evaluate their potential as non-invasive biomarkers for EO-CRC. Design: We performed metagenomic and metabolomic analyses, identified multiomics markers and constructed CRC classifiers for the discovery cohort with 130 late-onset CRC (LO-CRC), 114 EO-CRC subjects and age-matched healthy controls (97 LO-Control and 100 EO-Control). An independent cohort of 38 LO-CRC, 24 EO-CRC, 22 LO-Controls and 24 EO-Controls was analysed to validate the results. Results: Compared with controls, reduced alpha-diversity was apparent in both, LO-CRC and EO-CRC subjects. Although common variations existed, integrative analyses identified distinct microbiome–metabolome associations in LO-CRC and EO-CRC. Fusobacterium nucleatum enrichment and short-chain fatty acid depletion, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production characterises LO-CRC. In comparison, multiomics signatures of EO-CRC tended to be associated with enriched Flavonifractor plauti and increased tryptophan, bile acid and choline metabolism. Notably, elevated red meat intake-related species, choline metabolites and 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 controls. Conclusion: Our large-sample multiomics data suggest that altered microbiome–metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC. The potential of microbiome-derived biomarkers as promising non-invasive tools could be used for the accurate detection and distinction of individuals with EO-CRC.
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Compared with patients aged 50 years or older, those with early onset CRC usually present with more advanced disease and have different pathological features and CRC GOMS.
“Compared with patients of ≥50 years of age, those with early onset CRC usually present with more advanced disease, and have different pathological features and CRC GOMS83,84.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [84]
Early onset CRC GOMS is characterized by enrichment of F. plautii and increased metabolism of tryptophan, bile acids, and choline.
“The latter is characterized by an enrichment of F. plautii and increased metabolism of tryptophan, bile acids and choline.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [84]
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Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
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- Authors
- Kong, C., Liang, L., Liu, G., Du, L., Yang, Y., Liu, J., Shi, D., Li, X., & Ma, Y.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Guangdong Hongyuan Pukang Medical Technology Co., Ltd, Guangdong, China
- Second Hospital of Shandong University (CN)
- Fudan University Shanghai Cancer Center (CN)
- Corresponding author
- Ma, Yanlei
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2022-08-11
- Volume
- 72
- Issue
- 6
- Pages
- 1129-1142
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W4296580963
- Cited by
- 254
- References
- 60
- Citations by year
- 2026: 50 · 2025: 79 · 2024: 79 · 2023: 41 · 2022: 5
- FWCI
- 16.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fudan University Excellence 2025 Talent Cultivation Plan (for Dr. Yanlei Ma)
- CSCO-Roche Tumor Research Fund (No. Y-2019Roche-079)
- National Natural Science Foundation of China (81871964, 81920108026)
- Science and Technology Development Fund (19410713300)
- the Program of Shanghai Academic Research Leader (20XD1421200)
- the National Ten Thousand Plan Young Top Talents (for Dr. Yanlei Ma)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- early-onset colorectal cancer, late-onset colorectal cancer, gut microbiota, gut metabolome, microbiome-metabolome interactions, non-invasive biomarkers, Fusobacterium nucleatum, short-chain fatty acids, GABA synthesis, Flavonifractor plautii, tryptophan metabolism, bile acid metabolism, choline metabolism, red meat consumption, microbial enzymes
- MeSH terms
- Gastrointestinal Microbiome, Choline, Humans, Phenotype, Colorectal Neoplasms, Microbiota
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