Zhou MX, Zhao Y, Chu CL, Behera TR, Shen QQ, Xing YB. Diabetic gastrointestinal autonomic neuropathy: Integrating neuronal degeneration and gut microbial dysbiosis. World J Diabetes 2025; 16(9): 110053 [DOI: 10.4239/wjd.v16.i9.110053]
Corresponding Author of This Article
Quan-Quan Shen, MD, Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People's Hospital), Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. spring198457@sina.com
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/
Mei-Xia Zhou, Department of Nephrology, Tiantai People’s Hospital of Zhejiang Province (Tiantai Branch of Zhejiang Provincial People's Hospital), Hangzhou Medical College, Taizhou 317200, Zhejiang Province, China
Yu Zhao, Yu-Bo Xing, Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Chen-Ling Chu, Department of Clinical Medicine and Stomatology, Hangzhou Normal University, Hangzhou 310000, Zhejiang Province, China
Tapas Ranjan Behera, Department of Cancer Biology, Cleveland Clinic, Cleveland, OH 44195, United States
Quan-Quan Shen, Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Co-corresponding authors: Quan-Quan Shen and Yu-Bo Xing.
Author contributions: Zhou MX and Xing YB drafted the manuscript; Zhao Y and Behera TR revised the manuscript; Chu CL generated the figures; Xing YB and Shen QQ designed the research and revised the manuscript and both authors contributed equally to this study as co-corresponding authors; All authors have read and approved the final manuscript.
Supported by Natural Science Foundation of Zhejiang Province, No. LY23H050005; and Zhejiang Medical Technology Project, No. 2022RC009, No. 2023XY238, and No. 2024KY645.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: Quan-Quan Shen, MD, Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People's Hospital), Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. spring198457@sina.com
Received: May 28, 2025 Revised: June 25, 2025 Accepted: August 19, 2025 Published online: September 15, 2025 Processing time: 106 Days and 6.4 Hours
Abstract
Diabetic gastrointestinal autonomic neuropathy (DGAN) is a common and debilitating complication of diabetes, characterized by autonomic dysfunction in the gastrointestinal system. The complex pathophysiology of DGAN involves neuronal injury that is intrinsically linked to gut dysbiosis. Multiple factors, including hyperglycemia, oxidative stress, and inflammation, significantly contribute to neuronal damage, manifesting as symptoms such as delayed gastric emptying, diarrhea, and constipation. Recent studies have demonstrated that patients with diabetes experience substantial alterations in gut microbiota composition, potentially exacerbating gastrointestinal symptoms. Microbial metabolites may modulate neurotransmitter synthesis and release, directly affecting autonomic nerve function, while dysbiosis amplifies oxidative stress and inflammation, further compromising the enteric nervous system and worsening DGAN. Advances in multi-omics technologies now provide deeper insights into molecular mechanisms of DGAN and its interactions with microbiota. Early diagnosis leveraging biomarkers, gut microbiota analysis, and advanced imaging promises more effective interventions. Emerging therapeutic strategies targeting oxidative stress, inflammation, and gut microbiota represent promising approaches for managing DGAN. Future research should focus on large-scale, multi-ethnic studies and therapies targeting specific microbial metabolites to refine diagnosis and treatment approaches.
Core Tip: Diabetic gastrointestinal autonomic neuropathy (DGAN) represents a complex pathophysiological cascade driven by bidirectional interactions between hyperglycemia-induced neuronal injury and gut dysbiosis. Chronic hyperglycemia triggers oxidative stress, inflammatory pathways, and neurotrophic factor deficits, leading to damage of enteric neurons and glia. Concurrently, diabetes-associated dysbiosis reduces microbial diversity and beneficial metabolite production, which further exacerbates neuroinflammation and autonomic dysfunction. Advanced multi-omics approaches reveal these mechanisms, aiding early diagnosis through microbiome profiling and functional synaptic imaging. Therapeutic strategies targeting microbiota restoration, oxidative stress reduction, and neuroprotection show promise. Future research should prioritize large-scale clinical trials and metabolite-targeted interventions to advance personalized management of DGAN.
