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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1442506
This article is part of the Research Topic The Gut-Liver Axis: the Main Role of Microbiome in Liver Diseases View all 16 articles

Genetically predicted immune cells mediate the association between gut microbiota and autoimmune liver diseases

Provisionally accepted
Jikang Zhang Jikang Zhang 1Yiqi Hu Yiqi Hu 1Jin Xu Jin Xu 1Hua Shao Hua Shao 1Qingping Zhu Qingping Zhu 2*Hao Si Hao Si 3*
  • 1 General surgery department, Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
  • 2 Digestive Endoscopy Diagnosis and Treatment Center, Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
  • 3 Nanjing Pukou District Traditional Chinese Medicine Hospital, Nanjing, China

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

    Background: Increasing evidence suggests an association between gut microbiota and Autoimmune Liver Diseases (AILDs). However, causal inference remains controversial due to confounding bias in observational studies. Additionally, there is currently no clear evidence indicating that immune cells act as intermediate phenotypes in the pathogenesis of AILDs. This study utilizes the Mendelian Randomization (MR) method to investigate the causal relationships among gut microbiota, immune cells, and AILDs. Methods: Initially, we conducted a two-sample MR analysis to predict the causal relationships among 412 gut microbiota, 731 immune phenotypes, and AILDs. Subsequently, a series of sensitivity analyses were performed to validate the initial MR results and reverse MR analysis was conducted to exclude reverse causality. Finally, a two-step MR analysis was utilized to quantify the proportion of the impact of gut microbiota on AILDs mediated by immune cells. Results: Following rigorous MR analysis, our findings indicate that increased involvement of the gut microbiome in the superpathway of L-tryptophan biosynthesis is positively associated with an elevated risk of Autoimmune Hepatitis (AIH). The effect is partially mediated by the CD14+ CD16+ monocyte Absolute Count, which accounts for 17.47% of the total effect. Moreover, the species Ruminococcus obeum appears to mediate the development of Primary Sclerosing Cholangitis (PSC) through CD62L- CD86+ myeloid Dendritic Cell %Dendritic Cell, contributing to 32.47% of the total observed effect.Conclusion: Our study highlights the potential mediating mechanisms of immune cells in the causal relationship between the gut microbiome and AILDs. These insights provide a foundation for developing preventive strategies for AILDs in clinical practice. KEYWORD: Mendelian randomization, Autoimmune Hepatitis, Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, immune cells, gut microbiota

    Keywords: Mendelian randomization, Autoimmune Hepatitis, Primary biliary cholangitis, primary sclerosing cholangitis, immune cells, Gut Microbiota

    Received: 25 Jun 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Zhang, Hu, Xu, Shao, Zhu and Si. 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:
    Qingping Zhu, Digestive Endoscopy Diagnosis and Treatment Center, Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
    Hao Si, Nanjing Pukou District Traditional Chinese Medicine Hospital, Nanjing, China

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