Deciphering the Role of VIM, STX8, and MIF in Pneumoconiosis Susceptibility: A Mendelian Randomization Analysis of the Lung-Gut Axis and Multi-Omics Insights from European and East Asian Populations.

Chen Wei ZHANG; Bin Bin WAN; Yu Kai ZHANG; Tao XIONG; Yi Shan LI; Xue Sen SU; Gang LIU; Yang Yang WEI; Yuan Yuan SUN; Jing Fen ZHANG; Xiao YU; Yi Wei SHI

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Deciphering the Role of VIM, STX8, and MIF in Pneumoconiosis Susceptibility: A Mendelian Randomization Analysis of the Lung-Gut Axis and Multi-Omics Insights from European and East Asian Populations.

Author: Chen Wei ZHANG ¹ ; Bin Bin WAN ² ; Yu Kai ZHANG ³ ; Tao XIONG ³ ; Yi Shan LI ⁴ ; Xue Sen SU ⁴ ; Gang LIU ⁵ ; Yang Yang WEI ⁴ ; Yuan Yuan SUN ⁶ ; Jing Fen ZHANG ⁶ ; Xiao YU ⁴ ; Yi Wei SHI ⁴
Author Information

1. NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, The First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi, China;First School of Clinical Medicine, Shanxi Medical University, Taiyuan 030000, Shanxi, China.
2. Division of Planned Immunization, Yiwu Center for Disease Prevention and Control, Yiwu 322000, Zhejiang, China.
3. First School of Clinical Medicine, Shanxi Medical University, Taiyuan 030000, Shanxi, China.
4. NHC Key Laboratory of Pneumoconiosis, Shanxi Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, The First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi, China.
5. Department of Infection Control, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, Zhejiang, China.
6. Shanxi Medical University, Taiyuan 030000, Shanxi, China.
Publication Type:Journal Article
Keywords: Gut microbiota; Mendelian randomization; Multi-omics; Quantitative trait loci
MeSH: Humans; Male; East Asian People/genetics*; Europe; Gastrointestinal Microbiome; Lung; Macrophage Migration-Inhibitory Factors/metabolism*; Mendelian Randomization Analysis; Multiomics; Pneumoconiosis/microbiology*; Intramolecular Oxidoreductases
From: Biomedical and Environmental Sciences 2025;38(10):1270-1286
CountryChina
Language:English
Abstract: OBJECTIVE:Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR).
METHODS:We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes.
RESULTS:Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk.
CONCLUSIONS:This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.