Wang SY, Zhang MZ, Chen ZM, Li ZM, Xie CY, Yang GH, Xu B, Xu TC. Intestinal-related substances in obesity regulation: A comprehensive review. World J Gastrointest Pharmacol Ther 2025; 16(4): 111082 [DOI: 10.4292/wjgpt.v16.i4.111082]
Corresponding Author of This Article
Tian-Cheng Xu, 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
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Minireviews
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/
Shuai-Yan Wang, Meng-Zhe Zhang, Zi-Ming Chen, Zi-Mu Li, Cong-Yi Xie, 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: Shuai-Yan Wang and Meng-Zhe Zhang.
Co-corresponding authors: Bin Xu and Tian-Cheng Xu.
Author contributions: Wang SY was responsible for the idea and conceptual framework; Wang SY, Zhang MZ, Chen ZM, Li ZM, Xie CY and Xu TC wrote the first draft of the manuscript; Yang GH, Xu B and Xu TC reviewed the manuscript and critically revised it for important intellectual content; Xu B and Xu TC have played important and indispensable roles in the manuscript preparation as the co-corresponding authors; all authors have reviewed and approved the final version of the manuscript.
Supported by The National Natural Science Foundation, Youth Science Fund Project, No. 82305376; The Youth Talent Support Project of the China Acupuncture and Moxibustion Association, No. 2024-2026ZGZJXH-QNRC005; The 2024 Jiangsu Province Youth Science and Technology Talent Support Project, No. JSTJ-2024-380; and 2025 Jiangsu Provincial Science and Technology Think Tank Program Project, No. JSKX0125035.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest associated with the publication of this 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: Tian-Cheng Xu, 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: June 23, 2025 Revised: August 20, 2025 Accepted: November 17, 2025 Published online: December 5, 2025 Processing time: 166 Days and 0.1 Hours
Abstract
With the rising global obesity rates, particularly in industrialized nations, obesity has become an increasingly significant public health concern. This review analyzes 132 relevant studies published between 2020 and 2025, with a focus on the role of gut-derived substances in regulating obesity. These include gut hormones [such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY, cholecystokinin, and ghrelin], microbial metabolites [such as short-chain fatty acids (SCFA) and indole-3-propionic acid (IPA)], and neurotransmitters (such as serotonin and dopamine).The findings suggest that gut hormones play a crucial role in regulating appetite, glucose metabolism, and energy expenditure, and their dysregulation is closely linked to the development of obesity. Moreover, microbial metabolites like SCFA and IPA are strongly associated with metabolic health and significantly influence obesity-related mechanisms. This review also explores emerging therapeutic strategies, including GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, modulation of the gut microbiota, and fecal microbiota transplantation, all of which demonstrate promising potential in obesity management. However, challenges remain in optimizing these interventions, mitigating adverse effects, and establishing regulatory standards for microbiota-based therapies. Future research should aim to develop personalized, multi-targeted approaches to more effectively combat obesity and its associated metabolic disorders.
Core Tip: Gut hormones, microbial metabolites, and neurotransmitters such as 5-hydroxytryptamine (serotonin), short-chain fatty acids, and indolepropionic acid play crucial roles in regulating metabolism and obesity. Emerging therapies like glucagon-like peptide-1 receptor agonists and gut microbiota modulation show promise in addressing these factors. Future research should focus on personalized, multi-target approaches for effective obesity management, optimizing treatments, and understanding the diverse impacts of gut-derived substances on metabolic health.
