Zhang TT, Yao J, Zhang HM. Microbiota-metabolite signatures in metastatic colorectal cancer: Promise, pitfalls, and the path forward. World J Gastrointest Oncol 2026; 18(2): 115010 [DOI: 10.4251/wjgo.v18.i2.115010]
Corresponding Author of This Article
Han-Meng Zhang, MD, Department of Oncology, Huai’an Hospital of Huai’an City, No. 19 Shanyang Avenue, Huai’an 223299, Jiangsu Province, China. 15380666158@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
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/
World J Gastrointest Oncol. Feb 15, 2026; 18(2): 115010 Published online Feb 15, 2026. doi: 10.4251/wjgo.v18.i2.115010
Microbiota-metabolite signatures in metastatic colorectal cancer: Promise, pitfalls, and the path forward
Ting-Ting Zhang, Juan Yao, Han-Meng Zhang
Ting-Ting Zhang, Han-Meng Zhang, Department of Oncology, Huai’an Hospital of Huai’an City, Huai’an 223299, Jiangsu Province, China
Juan Yao, Department of Radiation Oncology, Huai’an Hospital of Huai’an City, Huai’an 223299, Jiangsu Province, China
Co-corresponding authors: Juan Yao and Han-Meng Zhang.
Author contributions: Zhang TT was responsible for conceptualization, methodology, data curation, and writing original draft; Yao J and Zhang HM were responsible for conceptualization, investigation, writing review and editing, supervision, methodology, validation, and supervision as co-corresponding authors; all of the authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
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: Han-Meng Zhang, MD, Department of Oncology, Huai’an Hospital of Huai’an City, No. 19 Shanyang Avenue, Huai’an 223299, Jiangsu Province, China. 15380666158@163.com
Received: October 9, 2025 Revised: November 5, 2025 Accepted: November 27, 2025 Published online: February 15, 2026 Processing time: 121 Days and 9.5 Hours
Abstract
This letter evaluates Deng et al study examining the gut microbiota and metabolite changes in metastatic colorectal cancer (CRC). The research used 16S rRNA sequencing and liquid chromatography-mass spectrometry metabolomics to investigate microbial and metabolic shifts in patients with metastatic vs non-metastatic CRC. The study reveals that CRC patients with metastasis exhibit significant differences in their gut microbiota and metabolites compared to non-metastatic patients. However, the study’s reliance on 16S rRNA sequencing presents inherent limitations, particularly with respect to species-level resolution. The sequencing depth may not have been sufficient to capture all relevant low-abundance taxa, as indicated by the rarefaction curves which did not fully plateau, potentially affecting the identification of differential species. It also identifies 91 differential metabolites, particularly those involved in nucleic acid, alkaloid, and lipid metabolism, which may contribute to metastasis progression. The findings suggest that microbiota and their metabolites play a critical role in CRC metastasis, offering potential targets for diagnosis and treatment. However, several limitations exist, including small sample size, single-center data, and a cross-sectional design that prevents causal conclusions. Additionally, the study lacks integration of key clinical factors such as dietary patterns and medication use, which could confound the results. Future research should expand these findings through multi-center studies with longer follow-up periods, incorporating more comprehensive clinical data and advanced analytical techniques to validate and refine the role of microbiota and metabolites in CRC metastasis. Despite its limitations, this study provides valuable insights into the microbiota-metabolite axis in CRC metastasis and opens potential avenues for future research. However, it is crucial to note that the metabolite identification was based on database matching rather than chemical standard validation. As such, these results should be considered putative annotations, with their accuracy requiring further confirmation through targeted analyses.
Core Tip: Deng et al explores the role of gut microbiota and metabolites in colorectal cancer (CRC) metastasis using 16S rRNA sequencing and liquid chromatography-mass spectrometry-based metabolomics. It identifies significant differences in microbial communities and metabolites between metastatic and non-metastatic CRC patients. The findings suggest that specific microbial taxa and metabolites may contribute to metastasis progression, offering potential biomarkers for diagnosis and treatment. Despite some limitations, such as small sample size and cross-sectional design, the study provides valuable insights into the microbiota-metabolite axis and its potential for therapeutic targeting in CRC.
