Xie FJ, Zhang M, Li WT, Zhou WY, Ma HB, Xu Y, Bi LM. Targeting gut microbiota: Potential mechanisms in the pathogenesis of type 2 diabetes mellitus and emerging translational intervention strategies. World J Diabetes 2026; 17(9): 122293 [DOI: 10.4239/wjd.122293]
Corresponding Author of This Article
Li-Ming Bi, MD, Professor, Department of Traditional Chinese Medicine Classics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, No. 8 Zhongnan West Road, Binhu District, Wuxi 214071, Jiangsu Province, China. biliming00@aliyun.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
review-article
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/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Xie FJ, Zhang M, Li WT, Zhou WY, Ma HB, Xu Y, Bi LM. Targeting gut microbiota: Potential mechanisms in the pathogenesis of type 2 diabetes mellitus and emerging translational intervention strategies. World J Diabetes 2026; 17(9): 122293 [DOI: 10.4239/wjd.122293]
Fu-Jian Xie, Li-Ming Bi, Department of Traditional Chinese Medicine Classics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Wuxi 214071, Jiangsu Province, China
Miao Zhang, Wan-Ting Li, Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai 200072, China
Wan-Ting Li, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
Wei-Ye Zhou, Hai-Bei Ma, School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518000, Guangdong Province, China
Yu Xu, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Co-first authors: Fu-Jian Xie and Miao Zhang.
Co-corresponding authors: Yu Xu and Li-Ming Bi.
Author contributions: Xie FJ and Zhang M were responsible for conceptualization, validation, writing-original draft, and equally contributed as co-first authors; Li WT was responsible for investigation, formal analysis, data curation, and visualization; Zhou WY and Ma HB were responsible for resources and project administration; Xu Y and Bi LM were responsible for supervision, writing-review and editing, and equally contributed as co-corresponding authors; all authors have read and agreed to the published version of the manuscript.
AI contribution statement: AI tools (specifically ChatGPT) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by Wuxi “Double Hundred” Young and Middle-aged Medical Top Talents Program, No. BJ2023065; and Jiangsu Provincial Administration of Traditional Chinese Medicine, No. ZZYB21.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Li-Ming Bi, MD, Professor, Department of Traditional Chinese Medicine Classics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, No. 8 Zhongnan West Road, Binhu District, Wuxi 214071, Jiangsu Province, China. biliming00@aliyun.com
Received: April 17, 2026 Revised: July 1, 2026 Accepted: July 28, 2026 Published online: September 15, 2026 Processing time: 138 Days and 11.5 Hours
Abstract
Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by insulin resistance and progressive impairment of β-cell function, accounting for the vast majority of diabetes cases worldwide. Beyond classic mechanisms such as ectopic fat deposition and chronic inflammation, increasing evidence indicates that the gut microbiota serves as a critical system regulating glucose homeostasis and plays a key role in the pathogenesis and progression of T2DM. T2DM is frequently accompanied by gut dysbiosis, characterized by an enrichment of pro-inflammatory and endotoxin-producing bacteria alongside a reduction in short-chain fatty acid-producing and barrier-maintaining microbes. This dysbiosis induces metabolic inflammation, disrupts the bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 signaling pathway, weakens the incretin response, and exacerbates insulin resistance. Conversely, restoring specific microbial functional modules can improve hyperglycemia, suggesting that functional dysregulation rather than mere compositional shifts lies at the disease core. This review examines primary mechanisms by which gut microbes promote or suppress T2DM. Crucially, we describe microbe-targeted intervention strategies, including dietary modulation, prebiotics/probiotics, fecal microbiota transplantation, pharmacotherapy, and traditional Chinese medicine approaches.
Core Tip: Increasing evidence indicates that gut microbiota plays a critical role in the development of type 2 diabetes mellitus (T2DM). Unlike previous reviews that primarily focus on microbial compositional alterations, this review highlights that functional dysregulation of the gut microbiota is the central driver of T2DM pathogenesis. We propose an integrated metabolic-immune-barrier-endocrine framework linking microbial metabolites, inflammation, intestinal barrier dysfunction, and endocrine signaling to glucose dysregulation. We further summarize emerging microbiota-targeted interventions and their translational potential for personalized T2DM management.
