The gut-brain axis in the context of colorectal cancer

The gut-brain axis (GBA) plays a pivotal role in the pathophysiology of colorectal cancer (CRC), influencing tumor progression, immune responses, and therapeutic outcomes. Bidirectional communication between the gut and the brain, mediated through microbial metabolites, neurotransmitters, and neural...

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Main Authors: Hao Wu, Kexin He, Hao Wang, Weihan Li, Ruixue Huo, Shu-Heng Jiang, Junli Xue
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Pharmacological Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1043661825002415
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author Hao Wu
Kexin He
Hao Wang
Weihan Li
Ruixue Huo
Shu-Heng Jiang
Junli Xue
author_facet Hao Wu
Kexin He
Hao Wang
Weihan Li
Ruixue Huo
Shu-Heng Jiang
Junli Xue
author_sort Hao Wu
collection DOAJ
description The gut-brain axis (GBA) plays a pivotal role in the pathophysiology of colorectal cancer (CRC), influencing tumor progression, immune responses, and therapeutic outcomes. Bidirectional communication between the gut and the brain, mediated through microbial metabolites, neurotransmitters, and neural signaling pathways, shapes the tumor microenvironment and systemic inflammation. CRC cells not only modify the gut microbiota but also release neuroactive molecules that influence neural circuits, further impacting tumor growth. The autonomic nervous system regulates gut motility, immune responses, and inflammation, contributing to CRC progression. The gut microbiome’s production of bioactive molecules, such as short-chain fatty acids and neurotransmitters, further modulates brain activity, promoting tumor metastasis and immune evasion. This review summarizes the complex interactions within the GBA and their implications for CRC, with a focus on immune modulation, microbial dysbiosis, and neuroimmune interactions. We highlight the therapeutic potential of targeting the GBA, including microbiome modulation, neurotransmitter-specific therapies, and psychological interventions, which could complement existing CRC treatments. Future research is essential to further elucidate the precise molecular mediators of the GBA and their impact on CRC biology, laying the groundwork for novel, targeted therapeutic strategies that could improve patient outcomes.
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spelling doaj-art-ad94b7eb62fd4b98b5efeb02a32ae2ca2025-08-20T03:10:20ZengElsevierPharmacological Research1096-11862025-07-0121710781610.1016/j.phrs.2025.107816The gut-brain axis in the context of colorectal cancerHao Wu0Kexin He1Hao Wang2Weihan Li3Ruixue Huo4Shu-Heng Jiang5Junli Xue6Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, PR ChinaDepartment of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, PR ChinaDepartment of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, PR ChinaDepartment of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, PR ChinaDepartment of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, PR ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, PR China; Corresponding authors.Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, PR China; Corresponding authors.The gut-brain axis (GBA) plays a pivotal role in the pathophysiology of colorectal cancer (CRC), influencing tumor progression, immune responses, and therapeutic outcomes. Bidirectional communication between the gut and the brain, mediated through microbial metabolites, neurotransmitters, and neural signaling pathways, shapes the tumor microenvironment and systemic inflammation. CRC cells not only modify the gut microbiota but also release neuroactive molecules that influence neural circuits, further impacting tumor growth. The autonomic nervous system regulates gut motility, immune responses, and inflammation, contributing to CRC progression. The gut microbiome’s production of bioactive molecules, such as short-chain fatty acids and neurotransmitters, further modulates brain activity, promoting tumor metastasis and immune evasion. This review summarizes the complex interactions within the GBA and their implications for CRC, with a focus on immune modulation, microbial dysbiosis, and neuroimmune interactions. We highlight the therapeutic potential of targeting the GBA, including microbiome modulation, neurotransmitter-specific therapies, and psychological interventions, which could complement existing CRC treatments. Future research is essential to further elucidate the precise molecular mediators of the GBA and their impact on CRC biology, laying the groundwork for novel, targeted therapeutic strategies that could improve patient outcomes.http://www.sciencedirect.com/science/article/pii/S1043661825002415Cancer neuroscienceNeural invasionCentral nervous systemGastrointestinal diseasesNeuroimmune modulation
spellingShingle Hao Wu
Kexin He
Hao Wang
Weihan Li
Ruixue Huo
Shu-Heng Jiang
Junli Xue
The gut-brain axis in the context of colorectal cancer
Pharmacological Research
Cancer neuroscience
Neural invasion
Central nervous system
Gastrointestinal diseases
Neuroimmune modulation
title The gut-brain axis in the context of colorectal cancer
title_full The gut-brain axis in the context of colorectal cancer
title_fullStr The gut-brain axis in the context of colorectal cancer
title_full_unstemmed The gut-brain axis in the context of colorectal cancer
title_short The gut-brain axis in the context of colorectal cancer
title_sort gut brain axis in the context of colorectal cancer
topic Cancer neuroscience
Neural invasion
Central nervous system
Gastrointestinal diseases
Neuroimmune modulation
url http://www.sciencedirect.com/science/article/pii/S1043661825002415
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