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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1447877

Exploring the causal relationship of gut microbiota in nonunion: a mendelian randomization analysis mediated by immune cell

Provisionally accepted
Yu Fei Yu Yu Fei Yu 1Hai Feng Gong Hai Feng Gong 2*Wei Ju Li Wei Ju Li 3*Mao Wu Mao Wu 1*Gang Hu Gang Hu 1*
  • 1 Wuxi Traditional Chinese Medicine Hospital, Wuxi, China
  • 2 The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
  • 3 Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China

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

    Background: Emerging research indicates that gut microbiota (GM) are pivotal in the regulation of immune-mediated bone diseases. Nonunion, a bone metabolic disorder, has an unclear causal relationship with GM and immune cells. This study aims to elucidate the causal relationship between GM and nonunion using Mendelian Randomization (MR) and to explore the mediating role of immune cells.Methods: Using a two-step, two-sample Mendelian randomization approach, this study explores the causal link between GM and nonunion, as well as the mediating role of immune cells in this relationship. Data were sourced from multiple cohorts and consortiums, including the MiBioGen consortium. GM data were derived from a recently published dataset of 473 gut microbiota, and nonunion data were obtained from genome-wide association studies (GWAS).Results: MR analysis identified 12 bacterial genera with protective effects against nonunion and 7 bacterial genera associated with a higher risk of nonunion, including Agathobacter sp000434275, Aureimonas, Clostridium M, Lachnospirales, Megamonas funiformis, and Peptoccia. Reverse MR analysis indicated that nonunion does not influence GM. Additionally, MR analysis identified 12 immune cell types positively associated with nonunion and 14 immune cell types negatively associated with nonunion. Building on these findings, we conducted mediation MR analysis to identify 24 crucial GM and immune cell-mediated relationships affecting nonunion. Notably, Campylobacter D, Megamonas funiformis, Agathobacter sp000434275, Lachnospirales, Clostridium E sporosphaeroides, and Clostridium M significantly regulated nonunion through multiple immune cell characteristics.To our knowledge, our research results are the first to emphasize a causal relationship between the gut microbiome and nonunion, potentially mediated by immune cells.The correlations and mediation effects identified in our study provide valuable insights into potential therapeutic strategies targeting the gut microbiome, informing global action plans.

    Keywords: Name: Yun-fei Yu gut microbiota, Nonunion, immune cell, Mendelian randomization, Instrumental variable

    Received: 14 Jun 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Yu, Gong, Li, Wu and Hu. 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:
    Hai Feng Gong, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong Province, China
    Wei Ju Li, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
    Mao Wu, Wuxi Traditional Chinese Medicine Hospital, Wuxi, China
    Gang Hu, Wuxi Traditional Chinese Medicine Hospital, Wuxi, 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.