Opinion Review
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 6, 2024; 12(1): 1-8
Published online Jan 6, 2024. doi: 10.12998/wjcc.v12.i1.1
Gut-targeted therapies for type 2 diabetes mellitus: A review
Tian-Cheng Xu, Yun Liu, Zhi Yu, Bin Xu
Tian-Cheng Xu, Yun Liu, Zhi Yu, Bin Xu, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Co-first authors: Tian-Cheng Xu and Yun Liu.
Co-corresponding authors: Zhi Yu and Bin Xu.
Author contributions: Yu Z and Xu B conceptualized and designed the research; Xu TC and Liu Y wrote the paper. Xu TC searched the literature, revised and submitted the early version of the manuscript with the focus on gut-targeted therapies for type 2 diabetes mellitus; Xu TC and Liu Y collaborated closely on basic research related to this review, which inspired the writing of this review; Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper; Yu Z and Xu B have played important and indispensable roles in the data interpretation and manuscript preparation as the co-corresponding authors; All the authors contributed to the initial writing and have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82074532, No. 82305376, and No. 81873238; the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine supported by the Subject of Academic Priority Discipline of Jiangsu Higher Education Institutions, No. ZYX03KF012; and the Postgraduate Research & Practice Innovation Program of Jiangsu Province, No. KYCX22_1963.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Bin Xu, MD, PhD, Director, Professor, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Nanjing 210023, Jiangsu Province, China. xubin@njucm.edu.cn
Received: August 27, 2023
Peer-review started: August 27, 2023
First decision: November 14, 2023
Revised: November 24, 2023
Accepted: December 18, 2023
Article in press: December 18, 2023
Published online: January 6, 2024

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. The global prevalence of T2DM has reached epidemic proportions, affecting approximately 463 million adults worldwide in 2019. Current treatments for T2DM include lifestyle modifications, oral antidiabetic agents, and insulin therapy. However, these therapies may carry side effects and fail to achieve optimal glycemic control in some patients. Therefore, there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM. The gut microbiota, which refers to the community of microorganisms that inhabit the human gut, has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity. Alterations in gut microbiota composition and diversity have been observed in T2DM patients, with a reduction in beneficial bacteria and an increase in pathogenic bacteria. This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function. Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM. One potential approach is the use of probiotics, which are live microorganisms that confer health benefits to the host when administered in adequate amounts. Several randomized controlled trials have demonstrated that certain probiotics, such as Lactobacillus and Bifidobacterium species, can improve glycemic control and insulin sensitivity in T2DM patients. Mechanisms may include the production of short-chain fatty acids, the improvement of gut barrier function, and the reduction of inflammation. Another gut-targeted therapy is fecal microbiota transplantation (FMT), which involves the transfer of fecal material from a healthy donor to a recipient. FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM. A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity. However, FMT carries potential risks, including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable. In addition to probiotics and FMT, other gut-targeted therapies are being investigated for the management of T2DM, such as prebiotics, synbiotics, and postbiotics. Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria, while synbiotics combine probiotics and prebiotics. Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host. The NIH SPARC program, or the Stimulating Peripheral Activity to Relieve Conditions, is a research initiative aimed at developing new therapies for a variety of health conditions, including T2DM. The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs, in order to regulate glucose levels in the body. The goal of this approach is to develop targeted, non-invasive therapies that can help patients better manage their diabetes. One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve, which plays an important role in regulating glucose metabolism. Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM. Gut-targeted therapies, such as probiotics and FMT, have shown potential for improving glycemic control and insulin sensitivity in T2DM patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies.

Keywords: Type 2 diabetes mellitus, Gastroenterology, Bacteria, Implanted device

Core Tip: Gut-targeted therapies, such as probiotics and fecal microbiota transplantation, have shown potential for improving glycemic control and insulin sensitivity in type 2 diabetes mellitus patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies. Although many invention patents have been formed and put into clinical practice for the treatment of hypoglycemia targeting the intestine, the increasing results of basic research still mean greater room for progress.