Xu X, Qu CK, Bao LL, Zhang YX, Wang WJ, Ye YQ. Bridge of imbalance: How does the brain-gut axis act as a catalyst for gastrointestinal tumors in aging. World J Gastroenterol 2026; 32(43): 121944 [DOI: 10.3748/wjg.121944]
Corresponding Author of This Article
Wen-Juan Wang, MM, Doctor, Department of Hematology and Oncology, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 1288 East Lushan Road, Beilun District, Ningbo 315800, Zhejiang Province, China. wwjwjbwsy@163.com
Research Domain of This Article
Oncology
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review-article
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Xu X, Qu CK, Bao LL, Zhang YX, Wang WJ, Ye YQ. Bridge of imbalance: How does the brain-gut axis act as a catalyst for gastrointestinal tumors in aging. World J Gastroenterol 2026; 32(43): 121944 [DOI: 10.3748/wjg.121944]
Xin Xu, Ling-Ling Bao, Wen-Juan Wang, Department of Hematology and Oncology, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, Ningbo 315800, Zhejiang Province, China
Xin Xu, Ling-Ling Bao, Wen-Juan Wang, Department of Hematology and Oncology, Beilun District People’s Hospital, Ningbo 315800, Zhejiang Province, China
Cheng-Kang Qu, Yu-Xuan Zhang, First School of Clinical Medicine, Zhengzhou University, Zhengzhou 450044, Henan Province, China
Ying-Quan Ye, Department of Gastrointestinal Medical Oncology, Fujian Cancer Hospital (Fujian Branch of Fudan University Shanghai Cancer Center), Fuzhou 350000, Fujian Province, China
Co-first authors: Xin Xu and Cheng-Kang Qu.
Co-corresponding authors: Wen-Juan Wang and Ying-Quan Ye.
Author contributions: Xu X and Qu CK have contributed equally to this study, as they are co-first authors; Xu X and Qu CK conceived the study; Bao LL, Zhang YX and Wang WJ searched the literature; Ye YQ evaluated the quality; Qu CK, Bao LL, Xu X drafted the manuscript; Ye YQ and Wang WJ revised the manuscript; Wang WJ and Ye YQ are co-corresponding authors, with equal responsibility for the integrity of the work and correspondence with the journal; all authors read and approved the final manuscript.
AI contribution statement: The authors confirm that no generative AI or AI-assisted technologies were used in the writing or preparation of this manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Wen-Juan Wang, MM, Doctor, Department of Hematology and Oncology, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 1288 East Lushan Road, Beilun District, Ningbo 315800, Zhejiang Province, China. wwjwjbwsy@163.com
Received: April 7, 2026 Revised: June 1, 2026 Accepted: June 23, 2026 Published online: November 21, 2026 Processing time: 175 Days and 2 Hours
Abstract
Aging is a complex biological process regulated by multiple factors. Its characteristics include shortening of telomere length, DNA damage, abnormal secretion of cytokines, and cellular oxidative damage. These changes eventually lead to the formation of tumor cells and the remodeling of the intestinal microenvironment. The brain-gut axis is a complex bidirectional communication network connecting the intestine and the central nervous system, composed of the nervous system, immune system, microbiota and their metabolites. It allows for information exchange between the intestine and the brain, influencing the function of the digestive system and brain activity. The remodeling of the brain-gut axis function caused by aging is an important catalyst promoting the development of gastrointestinal tumors. In aging, the dysbiosis of the intestinal microbiota, abnormal release of neurotransmitters, and neuroendocrine disorders will directly affect tumor occurrence through the brain-gut axis. In addition, aging can put the gastrointestinal tract in an inflammaging state, causing dysregulation of cancer immune. At the same time, the disruption of the circadian rhythm can affect the homeostasis of the gastrointestinal tract and promote tumor development. This review will specifically explore the factors that induce gastrointestinal tumors in aging through the components of the brain-gut axis and propose new therapeutic perspectives targeting the intestinal microbiota, neurotransmitters, immune conditions, and clock rhythm.
Core Tip: Aging remodels the brain-gut axis, creating a catalyst for gastrointestinal tumors. Key mechanisms include gut microbiota dysbiosis, neurotransmitter imbalance (e.g., 5-hydroxytryptamine, norepinephrine), neuroendocrine dysregulation, inflammaging, and circadian rhythm disruption. These factors remodel the tumor microenvironment, promote chronic inflammation, and drive tumorigenesis. Targeting the gut microbiota, neurotransmitter pathways, and circadian clocks offers emerging therapeutic strategies for aging-related gastrointestinal cancers.
