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World J Clin Cases. Mar 26, 2026; 14(9): 118295
Published online Mar 26, 2026. doi: 10.12998/wjcc.v14.i9.118295
Published online Mar 26, 2026. doi: 10.12998/wjcc.v14.i9.118295
Beyond glycemic control: How semaglutide reshapes intestinal neuroception via transforming growth factor-β/brain-derived neurotrophic factor signaling hubs
Hao-Yao Pan, Jia-Xin Liang, Wei-Wei Chen, Yi-Yang Sheng, Wen-Jing Zhang, Xue-Wen Zhu, Shuai-Yan Wang, Bin Xu, Tian-Cheng Xu, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Guan-Hu Yang, Department of Specialty Medicine, Ohio University, Athens, OH 45701, United States
Co-first authors: Hao-Yao Pan and Jia-Xin Liang.
Co-corresponding authors: Bin Xu and Tian-Cheng Xu.
Author contributions: Pan HY and Liang JX conceptualized and designed this review; Pan HY, Liang JX, Chen WW, Sheng YY, Zhang WJ and Zhu XW wrote the first draft of the manuscript; Pan HY was responsible for the core conceptualization and overall framework, while Liang JX was responsible for the creation of figures in the initial draft, both authors contributed significantly to the writing of the core content of the manuscript and coordinated the writing process, making essential and irreplaceable contributions to the completion of the project, and thus qualified as the co-first authors of the paper; Wang SY was responsible for language polishing and linguistic refinement of the manuscript; Yang GH provided overall guidance on the research direction and academic framework of the review; Xu B and Xu TC served as the co-corresponding authors, playing key roles in quality control, academic depth enhancement, and final manuscript coordination; Xu B applied for and secured funding for the research project, playing a crucial role in the overall design and quality control, ensuring the academic value and publication quality of the review; Xu TC focused on the academic depth and content rigor of the review, assuming key responsibilities for academic oversight, coordinating feedback from all authors on revised versions, leading responses to reviewer comments during the submission process, and guiding further improvements to the manuscript, ensuring the academic quality and publication standards of the review. All authors have reviewed and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 82305376; the Young Talent Support Program of the China Association for Acupuncture-Moxibustion, No. 2024-2026ZGZJXH-QNRC005; the 2024 Jiangsu Provincial Young Scientific and Technological Talent Support Program, No. JSTJ-2024-380; and Talent Cultivation Program for Young Researchers, Key Laboratory of the Ministry of Education Project, No. zyqt202501, and No. zyqt202503.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Tian-Cheng Xu, MD, PhD, Academic Fellow, Professor, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China. xtc@njucm.edu.cn
Received: December 29, 2025
Revised: January 24, 2026
Accepted: February 26, 2026
Published online: March 26, 2026
Processing time: 85 Days and 17.7 Hours
Revised: January 24, 2026
Accepted: February 26, 2026
Published online: March 26, 2026
Processing time: 85 Days and 17.7 Hours
Core Tip
Core Tip: Semaglutide,a leading glucagon-like peptide-1 receptor agonist, reshapes gut-brain communication by bidirectionally modulating the transforming growth factor-β/brain-derived neurotrophic factor signaling axis in the gut. It promotes neuroprotective brain-derived neurotrophic factor via phosphatidylinositol 3-kinase/protein kinase B/cyclic adenosine monophosphate-response element-binding protein while suppressing profibrotic transforming growth factor-β/Smad signaling. Combined with beneficial shifts in gut microbiota and anti-inflammatory effects, this action remodels enteric neural perception, extending its therapeutic potential beyond metabolism to neuropsychiatric and neurodegenerative disorders.