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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Gut Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1442603
This article is part of the Research Topic Insights in Gut Endocrinology View all 5 articles

Causal relationships between the gut microbiota, inflammatory cytokines, and alcoholic liver disease: a Mendelian randomization analysis

Provisionally accepted
SHANZHENG LI SHANZHENG LI 1*Cheng Zhou Cheng Zhou 2Tong Liu Tong Liu 1Lihui Zhang Lihui Zhang 1Sutong Liu Sutong Liu 1Qing Zhao Qing Zhao 1Jiangkai Liu Jiangkai Liu 1Wenxia Zhao Wenxia Zhao 1
  • 1 Henan University of Chinese Medicine, Zhengzhou, China
  • 2 Changzhou Traditional Chinese Medicine Hospital, Changzhou, Jiangsu Province, China

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

    Objective: Previous studies have suggested a potential association between gut microbiota and the development of alcohol-related liver disease (ALD). However, the causal relationship between gut microbiota and ALD, as well as the role of inflammatory cytokines as mediators, remains unclear. This study aims to explore the causal relationship between gut microbiota and ALD using Mendelian randomization (MR) methods, and to analyze the mediating role of inflammatory cytokines.Methods: Gut microbiota, 91 inflammatory cytokines, and ALD were identified from summary data of large-scale genome-wide association studies (GWAS). MR was employed to investigate the causal relationship between gut microbiota, cytokines, and ALD, with the inverse variance-weighted method (IVW) as the primary statistical approach. Additionally, we examined whether inflammatory cytokines act as mediating factors in the pathway from gut microbiota to ALD.The IVW results confirmed two positive and one negative causal effect between genetic liability in the gut microbiota and ALD. Escherichia coli (P= 0.003) was identified as a protective factor for ALD, while Roseburia hominis (P=0.023) and Family Porphyromonadaceae (P=0.038) were identified as risk factors for ALD. Furthermore, there were five positive and two negative causal effects between inflammatory cytokines and ALD, with CUB domain-containing protein 1 (P= 0.035), Macrophage colony-stimulating factor 1 (P=0.047), Cystatin D (P = 0.035), Fractalkine (P=0.000000038), Monocyte chemoattractant protein-1 (P=0.004) positively associated with ALD onset. CD40L receptor (P= 0.044) and Leukemia inhibitory factor (P = 0.024) exhibited protective effects against ALD. Mediation MR analysis indicated that CUB domain-containing protein 1 (mediation proportion=1.6%, P=0.035), Cystatin D (mediation proportion=1.5%, P=0.012), and Monocyte chemoattractant protein-1 (mediation proportion=3.3%, P=0.005) mediated the causal effect of Roseburia hominis on ALD.In conclusion, our study supports a causal relationship among gut microbiota, inflammatory cytokines and ALD, with inflammatory cytokines potentially acting as mediating factors in the pathway from gut microbiota to ALD.

    Keywords: Mendelian randomization, Gut Microbiota, inflammatory cytokines, alcoholic liver disease, causal relationship

    Received: 02 Jun 2024; Accepted: 01 Oct 2024.

    Copyright: © 2024 LI, Zhou, Liu, Zhang, Liu, Zhao, Liu and Zhao. 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: SHANZHENG LI, Henan University of Chinese Medicine, Zhengzhou, China

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