ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1632406
Causal Relationship Between Gut Microbiota and Diabetic Neuropathy: A Mendelian Randomization and 16S rRNA Sequencing
Provisionally accepted
- 1Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
- 2Department of Endocrinology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Objectives: Evidence suggests a link between gut microbiota and diabetes mellitus, yet the specific role in diabetic peripheral neuropathy (DPN) remains elusive. The study aims to explore the association through Mendelian randomization and 16S rRNA gene sequencing analysis. Materials and methods: Mendelian randomization (MR) analysis was employed to investigate the causal association between gut microbiota and diabetic neuropathy. Diabetes mellitus (DM) and DPN mice models were developed via high-fat diet (HFD) feeding followed by intraperitoneal streptozotocin (STZ) administration at 30 mg/kg (DM group) or 60 mg/kg (DPN group). The occurrence of diabetic neuropathy was determined by evaluating pain-related behavioral parameters in mice. Additionally, fecal samples from mice and patients with diabetic neuropathy were collected, and 16S rDNA sequencing was performed to analyze the composition of gut microbiota. Results: Mendelian randomization analysis identified 14 gut microbiota species exhibiting a causal relationship with diabetic neuropathy. In animal studies, diabetic neuropathy mice exhibited decreased mechanical pain thresholds and reduced thermal withdrawal latency. Sequencing analyses further revealed significant alterations in gut microbiota composition in both DPN mice and DPN patients compared to control group. Conclusion: This study integrates Mendelian randomization analysis with 16S rRNA fecal assessments from animal models and clinical patients, revealing that gut microbiota imbalances may contribute to diabetic neuropathy development and providing novel insights for its prevention and therapeutic strategies.
Keywords: Gut Microbiota, Mendelian randomization, Diabetic peripheral neuropathy, 16S rRNAgene Sequencing, Diabetes Mellitus
Received: 21 May 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Hu, Liang, Lv, Mu, Wang, Huang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dingbang Huang, Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
Dezhao Liu, Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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