肠道微生物群和口腔扁平苔藓之间的因果关系：来自孟德尔随机化研究的见解

The Causal Relationship between Gut Microbiota and Oral Lichen Planus: Insights from Mendelian Randomization Studies

摘要: 背景与目的：口腔扁平苔藓(Oral lichen planus, OLP)是一种口腔黏膜慢性炎症性疾病。先前的研究表明，肠道微生物群在调节宿主免疫系统和炎症反应中具有重要作用，并与多种慢性炎症性疾病密切相关。然而，肠道菌群与OLP之间的因果关系尚未明确。本研究利用孟德尔随机化(MR)探索GM与OLP的因果关系，为潜在的发病机制和治疗策略提供新的视角。方法：本研究利用双样本(MR)方法探讨肠道菌群与OLP风险之间的潜在因果关系。肠道菌群遗传数据来源于MiBioGen联盟的全基因组关联研究(GWAS)，包括18,340名欧洲血统参与者，涵盖119个属水平的菌群分类。OLP的GWAS数据来自FinnGen生物库(795例OLP患者和499,553名对照)。采用逆方差加权(IVW)、MR-Egger、加权中位数、简单模式和加权模式等多种方法，通过计算比值比(OR)和置信区间(CI)评估因果关系，并使用MR-Egger截距检验、Cochran’s Q检验和留一法分析进行敏感性分析以确保结果的稳健性。结果：IVW方法显示，Subdoligranulum (OR = 0.548, 95% CI: 0.321~0.937, p = 0.028)、Family XIII UCG001 (OR = 0.583, 95% CI: 0.346~0.982, p = 0.043)、Prevotella7 (OR = 0.766, 95% CI: 0.589~0.995, p = 0.046)和Intestinibacter (OR = 0.616, 95% CI: 0.407~0.933, p = 0.022)与OLP风险降低相关，而Ruminococcaceae UCG009 (OR = 1.459, 95% CI: 1.037~2.054, p = 0.030)与OLP风险增加相关。敏感性分析未发现显著的异质性或多效性(p > 0.05)，留一法分析表明结果稳健。结论：本研究通过孟德尔随机化分析首次揭示了肠道菌群与OLP风险之间的潜在因果关系。结果表明，Subdoligranulum、Family XIII UCG001、Prevotella7和Intestinibacter可能具有保护作用，而Ruminococcaceae UCG009则与OLP风险增加相关。

Abstract: Background and Objectives: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. Previous studies have indicated that the gut microbiota plays a crucial role in regulating the host immune system and inflammatory responses, and is closely associated with various chronic inflammatory diseases. However, the causal relationship between the gut microbiota and OLP remains unclear. This study utilized Mendelian randomization (MR) to explore the causal relationship between the gut microbiota (GM) and OLP, providing new insights into potential pathogenesis and therapeutic strategies. Methods: This study employed a two-sample MR approach to investigate the potential causal relationship between the gut microbiota and OLP risk. The gut microbiota genetic data were sourced from the MiBioGen consortium’s genome-wide association study (GWAS), which included 18,340 participants of European ancestry and covered 119 genera-level microbial taxa. The GWAS data for OLP came from the FinnGen biobank (795 OLP patients and 499,553 controls). Various methods, including inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were applied to estimate causal relationships by calculating odds ratios (OR) and confidence intervals (CI). Sensitivity analyses were conducted using MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis to ensure the robustness of the results. Results: The IVW method revealed that Subdoligranulum (OR = 0.548, 95% CI: 0.321~0.937, p = 0.028), Family XIII UCG001 (OR = 0.583, 95% CI: 0.346~0.982, p = 0.043), Prevotella7 (OR = 0.766, 95% CI: 0.589~0.995, p = 0.046), and Intestinibacter (OR = 0.616, 95% CI: 0.407~0.933, p = 0.022) were associated with a decreased risk of OLP, while Ruminococcaceae UCG009 (OR = 1.459, 95% CI: 1.037~2.054, p = 0.030) was associated with an increased risk of OLP. Sensitivity analysis did not reveal significant heterogeneity or pleiotropy (p > 0.05), and the leave-one-out analysis indicated robust results. Conclusion: This study, through Mendelian randomization analysis, is the first to reveal a potential causal relationship between the gut microbiota and OLP risk. The findings suggest that Subdoligranulum, Family XIII UCG001, Prevotella7, and Intestinibacter may have a protective effect, while Ruminococcaceae UCG009 is associated with an increased risk of OLP.