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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Gut Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1388927
This article is part of the Research Topic Exploring the New Biomarkers and Clinical Indicators for Diabetes: Insights from Real-World Studies View all 9 articles

Causal Effects of Gut Microbiota on Diabetic Neuropathy: A Two-Sample Mendelian Randomization Study

Provisionally accepted
  • 1 Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 2 The First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 3 Department of Pharmacology, School of Basic Medicine, Shanxi Medical University, Taiyuan, Shaanxi, China
  • 4 Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, China

The final, formatted version of the article will be published soon.

    Objective: Previous observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN.Methods: We conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables.Results: The IVW analysis indicated that Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity.Our study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy.

    Keywords: Diabetic neuropahy, Mendelian randomization, Gut Microbiota, GWAS - genome-wide association study, Diabetic autonomic nervous system neuropathy, diabetic polyneruopathy

    Received: 20 Feb 2024; Accepted: 17 Jul 2024.

    Copyright: © 2024 Xu, Hao, Qi, Wu, Li, Yang, Zhang 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:
    Jingxuan Hao, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
    Yijie Qi, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
    Yi Zhang, Department of Pharmacology, School of Basic Medicine, Shanxi Medical University, Taiyuan, Shaanxi, China
    Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

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