Deng P, Lin H, Zeng H, Guo F. Gut microbiota and metabolite changes in metastatic colorectal cancer via 16S rRNA and metabolomics. World J Gastrointest Oncol 2025; 17(10): 111509 [PMID: 41114121 DOI: 10.4251/wjgo.v17.i10.111509]
Corresponding Author of This Article
Feng Guo, MD, Doctor, Department of Interventional Diagnosis and Treatment, The Central Hospital of Yongzhou, No. 396 Yiyun Road, Lengshuitan District, Yongzhou 425002, Hunan Province, China. search_gf@163.com
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Gastroenterology & Hepatology
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Observational Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Oct 15, 2025 (publication date) through Oct 25, 2025
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World Journal of Gastrointestinal Oncology
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1948-5204
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Deng P, Lin H, Zeng H, Guo F. Gut microbiota and metabolite changes in metastatic colorectal cancer via 16S rRNA and metabolomics. World J Gastrointest Oncol 2025; 17(10): 111509 [PMID: 41114121 DOI: 10.4251/wjgo.v17.i10.111509]
World J Gastrointest Oncol. Oct 15, 2025; 17(10): 111509 Published online Oct 15, 2025. doi: 10.4251/wjgo.v17.i10.111509
Gut microbiota and metabolite changes in metastatic colorectal cancer via 16S rRNA and metabolomics
Pan Deng, Hua Lin, Hu Zeng, Feng Guo
Pan Deng, Hua Lin, Department of General Surgery, Xiangya Changde Hospital, Changde 415009, Hunan Province, China
Hu Zeng, Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Jinan University, Dongguan 523560, Guangdong Province, China
Feng Guo, Department of Interventional Diagnosis and Treatment, The Central Hospital of Yongzhou, Yongzhou 425002, Hunan Province, China
Co-first authors: Pan Deng and Hua Lin.
Co-corresponding authors: Hu Zeng and Feng Guo.
Author contributions: Zeng H and Guo F designed the study; While Deng P and Lin H executed the research.
Institutional review board statement: The study protocol was approved by the Institutional Ethics Committee of Xiangya Changde Hospital (No. 2021-06).
Informed consent statement: All participants in this study voluntarily provided their written informed consent.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: To protect patient privacy, research data will not be made public. If necessary, please contact the corresponding author to obtain it.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Guo, MD, Doctor, Department of Interventional Diagnosis and Treatment, The Central Hospital of Yongzhou, No. 396 Yiyun Road, Lengshuitan District, Yongzhou 425002, Hunan Province, China. search_gf@163.com
Received: July 8, 2025 Revised: August 20, 2025 Accepted: September 24, 2025 Published online: October 15, 2025 Processing time: 97 Days and 23.8 Hours
Abstract
BACKGROUND
Distant metastasis causes most colorectal cancer (CRC) deaths. Gut microbiota (GM) dysbiosis and altered metabolites drive metastasis progression, serving as potential diagnostic biomarkers.
AIM
To investigate alterations in GM and metabolites between patients with non-metastatic and distant metastatic CRC.
METHODS
According to the inclusion criteria, fresh fecal samples were collected from 14 non-metastatic CRC patients and 15 distant metastatic CRC patients. We performed 16S rRNA sequencing to analyze the composition, diversity, and differential abundance of GM, along with predictive functional profiling of microbial communities. Additionally, all samples underwent liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomic sequencing to identify metabolic changes and predict their biological functions.
RESULTS
The cohort comprised 16 non-metastatic CRC patients (designated as the S group) and 16 distant metastatic CRC patients (designated as the DZ group). Sequence analysis (16S rRNA) identified a total of 35016 operational taxonomic units (OTUs) across both groups (16886 OTUs in the S group; 16270 in the DZ group; 1860 shared between groups). Inter-group microbial diversity analysis revealed notable differences in the β-diversity group (P < 0.05). Comparative analysis of GM revealed significant taxonomic composition differences between groups (P < 0.05), with higher relative abundances of Butyricicoccus, Ruminococcus_1, Coprococcus_2 in the S group, Pyramidobacter, Christensenellaceae_R-7_group, and Romboutsia in the DZ group (all P < 0.05). Functional analysis of differential microbiota revealed predominant enrichment in metabolic pathways. LC-MS-based untargeted metabolomics detected 91 differential metabolites in both positive and negative ionization modes. GM-derived metabolites showed significant alterations in the DZ group. Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database analyses revealed associated pathways involving nucleic acids, organic heterocyclic compounds, alkaloids, lipids/lipid-like molecules, and nucleotides. These metabolites may function synergistically, as evidenced by positive correlations between diazoxide, hydroquinidine, aurapten, and triptophenolide. Differential metabolites were primarily involved in aminoacyl-tRNA biosynthesis, central carbon metabolism in cancer, phenylalanine metabolism, vitamin B6 metabolism, and protein digestion and absorption pathways.
CONCLUSION
GM and microbial metabolites differ significantly between CRC patients with distant metastasis and those without metastasis. Metabolites involved in nucleic acid, alkaloid, and lipid metabolism pathways potentially contribute to distant metastasis in CRC.
Core Tip: Colorectal cancer patients with different metastatic statuses exhibit distinct gut microbiota and metabolite profiles. These differences may contribute to cancer progression and metastasis, providing potential biomarkers for early diagnosis and therapeutic targets.
