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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1430675

Genetic associations between gut microbiota and type 2 diabetes mediated by plasma metabolites: a mendelian randomization study

Provisionally accepted
XuWen Zheng XuWen Zheng Maobing Chen Maobing Chen *Yi Zhuang Yi Zhuang *Liang Zhao Liang Zhao *Yongjun Qian Yongjun Qian *Jin Xu Jin Xu *
  • Changzhou Wujin People's Hospital, Changning, China

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

    Background Numerous research studies have indicated a possible association between type 2 diabetes (T2DM) and gut microbiota. To explore specific metabolic pathways connecting gut microbiota and T2DM, we employed mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) techniques.This research utilized data from genome-wide association studies (GWAS) that are publicly accessible. We evaluated the genetic correlation between gut microbiota and T2DM using LDSC. Causality was primarily determined through the inverse variance weighted (IVW) method. To verify the robustness of our results, we conducted sensitivity analyses using several approaches, including the weighted median, MR-Egger, and MR-PRESSO. We integrated summary effect estimates from LDSC, along with forward and reverse MR, into a meta-analysis for T2DM using various data sources. Additionally, mediation analysis was performed to explore the impact of plasma metabolites on the relationship between gut microbiota and T2DM.RuminococcaceaeUCG005 (Rg = -0.26, Rg_P = 2.07×10 -4 ) and T2DM. Moreover, the forward MR analysis identified genus RuminococcaceaeUCG010 (OR = 0.857, 95% CI 0.795, 0.924; P = 6.33×10 -5 ) and order Clostridiales (OR = 0.936, 95% CI 0.878, 0.997; P = 0.039) as being significantly associated with a decreased risk of T2DM. The analysis also highlighted several plasma metabolites as significant mediators in these relationships, with metabolites like octadecadienedioate (C18:2-DC) and branched chain 14:0 dicarboxylic acid being notably involved.The findings demonstrate a significant impact of gut microbiota on T2DM via plasma metabolites, suggesting potential metabolic pathways for therapeutic targeting. This study enhances our understanding of the microbiota's role in T2DM pathogenesis and supports the development of microbiota-based interventions.

    Keywords: type 2 diabetes, Gut Microbiota, Plasma metabolites, Mendelian randomization, linkage disequilibrium score regression, Meta-analysis

    Received: 10 May 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Zheng, Chen, Zhuang, Zhao, Qian and Xu. 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:
    Maobing Chen, Changzhou Wujin People's Hospital, Changning, China
    Yi Zhuang, Changzhou Wujin People's Hospital, Changning, China
    Liang Zhao, Changzhou Wujin People's Hospital, Changning, China
    Yongjun Qian, Changzhou Wujin People's Hospital, Changning, China
    Jin Xu, Changzhou Wujin People's Hospital, Changning, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.