Wang GL, Deng H, Wang G, Qu NN. Mechanisms of the gut-lung axis in regulating lung metastasis of colorectal cancer and advances in traditional Chinese medicine intervention. World J Gastrointest Oncol 2026; 18(10): 123494 [DOI: 10.4251/wjgo.123494]
Corresponding Author of This Article
Ni-Ni Qu, Chief Physician, Respiratory and Critical Care Medicine Department 1/Pulmonary Disease Department 1, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine/Liaoning University of Traditional Chinese Medicine, No. 33 Beiling Street, Huanggu District, Shenyang 110000, Liaoning Province, China. qvnini@sina.com
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Gastroenterology & Hepatology
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review-article
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Wang GL, Deng H, Wang G, Qu NN. Mechanisms of the gut-lung axis in regulating lung metastasis of colorectal cancer and advances in traditional Chinese medicine intervention. World J Gastrointest Oncol 2026; 18(10): 123494 [DOI: 10.4251/wjgo.123494]
World J Gastrointest Oncol. Oct 15, 2026; 18(10): 123494 Published online Oct 15, 2026. doi: 10.4251/wjgo.123494
Mechanisms of the gut-lung axis in regulating lung metastasis of colorectal cancer and advances in traditional Chinese medicine intervention
Guo-Li Wang, Hu Deng, Ge Wang, Ni-Ni Qu
Guo-Li Wang, Respiratory and Critical Care Medicine Department 3/Pulmonary Disease Department 3, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine/Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China
Hu Deng, Respiratory and Critical Care Medicine Department 1/Pulmonary Disease Department 1, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China
Ge Wang, Department of Spleen and Stomach Oncology, Liaoning University of Traditional Chinese Medicine Hospital Subsidiary Fourth, Shenyang 110101, Liaoning Province, China
Ni-Ni Qu, Respiratory and Critical Care Medicine Department 1/Pulmonary Disease Department 1, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine/Liaoning University of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China
Co-first authors: Guo-Li Wang and Hu Deng.
Co-corresponding authors: Ge Wang and Ni-Ni Qu.
Author contributions: Wang GL and Deng H contributed equally to this manuscript and are co-first authors. Wang GL and Deng H contributed to conceptualization, data curation, methodology, software, and writing - original draft; Wang G contributed to formal analysis, project administration, visualization; Qu NN contributed to investigation, supervision, validation, and writing - review & editing. Wang G and Qu NN contributed equally to this manuscript and are co-corresponding authors.
AI contribution statement: This manuscript was prepared without the use of any generative AI or large language models.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ni-Ni Qu, Chief Physician, Respiratory and Critical Care Medicine Department 1/Pulmonary Disease Department 1, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine/Liaoning University of Traditional Chinese Medicine, No. 33 Beiling Street, Huanggu District, Shenyang 110000, Liaoning Province, China. qvnini@sina.com
Received: May 19, 2026 Revised: June 23, 2026 Accepted: August 10, 2026 Published online: October 15, 2026 Processing time: 124 Days and 17.2 Hours
Abstract
Pulmonary metastasis is a major cause of mortality in patients with colorectal cancer (CRC), but the underlying mechanisms remain incompletely understood. The gut-lung axis, which links the gut microbiota to lung homeostasis, has emerged as a key regulator of CRC progression and metastasis. Traditional Chinese medicine (TCM), based on the classical theory of the “interior-exterior relationship between the lung and large intestine”, may exert therapeutic effects through modulation of this axis. This review aimed to summarize the mechanisms by which the gut-lung axis regulates CRC pulmonary metastasis and to evaluate TCM-based interventions targeting this axis. A systematic search was conducted in PubMed, Web of Science, and China National Knowledge Infrastructure up to March 2026. Clinical and preclinical studies were included. Gut microbiota dysbiosis, characterized by enrichment of Faecalibacterium and enterotoxigenic Bacteroides fragilis, promotes epithelial-mesenchymal transition (EMT), remodels the pre-metastatic niche (PMN), and contributes to chemoresistance. Exosomes carrying specific microRNAs and circular RNAs can reach the lungs and create a microenvironment favorable for metastasis. Gut-derived immune cells, particularly T helper 17 and regulatory T cells, migrate to the lungs and shape local immune responses. In addition, the gut-lung leak axis driven by lipopolysaccharide/Toll-like receptor 4 signaling exacerbates pulmonary inflammation. TCM formulas, including Si-Jun-Zi decoction and combinations of Sophora japonica and Scutellaria baicalensis, as well as active compounds such as geniposide, berberine, and Astragalus polysaccharides, may restore microbial diversity, repair intestinal barrier function, inhibit EMT, and regulate exosome release. However, clinical evidence remains limited, and substantial translational challenges persist. The gut-lung axis represents a promising therapeutic target for CRC lung metastasis. Although TCM may regulate this axis through multiple mechanisms, current evidence is predominantly preclinical. Further mechanistic studies, particularly those clarifying causal relationships among microbial taxa, exosomal cargoes, and lung PMN formation, are needed before reliable clinical translation can be achieved. Well-designed randomized controlled trials remain essential for validating TCM-based interventions.
Core Tip: This review has three main objectives: (1) To analyze the molecular and cellular mechanisms by which the gut-lung axis regulates lung metastasis of colorectal cancer; (2) To critically summarize the evidence for traditional Chinese medicine therapies targeting this axis; and (3) To identify knowledge gaps and propose future research directions. Our main focus is on preclinical studies, as human data is still scarce, but we also discuss the challenges in translational research and the potential of microbiome-based biomarkers.
