Table_1_The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study.xlsx

BackgroundAccumulating evidence shows that dysregulation of intestinal flora is associated with inflammatory skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and rosacea (ROS). However, the causality is still unclear.
ObjectivesTo study the underlying causality between gut microbiota (GM) and AD, PSO, and ROS, a bi-directional two-sample Mendelian randomization (2SMR) analysis was conducted.
MethodsSummary statistics of gut microbiota, AD, PSO, and ROS were extracted from large-scale genome-wide association studies (GWASs). In 2SMR analysis, in addition to the inverse variance weighted as the principal method for evaluating causal association, four different methods were also used. Sensitivity analysis and reverse 2SMR study were implemented to evaluate the robustness of 2SMR results or reverse causal relationship, respectively.
ResultsA total of 24 specific gut microbiota species related to AD, PSO, and ROS were identified by 2SMR analysis. After using the Bonferroni method for multiple testing correction, family FamilyXIII (ID: 1957) [OR = 1.28 (1.13, 1.45), p = 9.26e−05] and genus Eubacteriumfissicatenagroup (ID: 14373) [OR = 1.20 (1.09, 1.33), p = 1.65e−04] were associated with an increased risk for AD and PSO, respectively. The genus Dialister showed a negative association, suggesting a protective role against both atopic dermatitis and rosacea. Our reverse 2SMR analysis indicated no reverse causality between these inflammatory skin diseases and the identified gut microbiota.
ConclusionsIn summary, this study provided evidence for the causality between GM and inflammatory skin diseases. These findings suggested that supplementing specific bacterial taxa may be an effective therapy for AD, PSO, and ROS.

研究背景：越来越多的研究证据表明，肠道菌群失调与炎症性皮肤病存在关联，具体包括特应性皮炎（atopic dermatitis，AD）、银屑病（psoriasis，PSO）以及玫瑰痤疮（rosacea，ROS）。但二者之间的因果关联仍未明确。
研究目的：本研究旨在明确肠道菌群（gut microbiota，GM）与特应性皮炎、银屑病及玫瑰痤疮之间的潜在因果关联，采用双向两样本孟德尔随机化（bidirectional two-sample Mendelian randomization，2SMR）分析方法开展研究。
研究方法：本研究从大规模全基因组关联研究（genome-wide association studies，GWASs）中提取肠道菌群、特应性皮炎、银屑病及玫瑰痤疮的汇总统计数据。在2SMR分析中，除以逆方差加权法作为评估因果关联的主要方法外，同时采用了4种不同的分析方法。本研究分别通过敏感性分析与反向2SMR分析，来验证2SMR结果的稳健性以及潜在的反向因果关联。
研究结果：本研究通过2SMR分析共鉴定出24种与特应性皮炎、银屑病及玫瑰痤疮相关的特定肠道菌群。经邦费罗尼法进行多重检验校正后，XIII科（ID: 1957）[比值比（odds ratio，OR）= 1.28 (95%置信区间: 1.13, 1.45), p = 9.26×10^-5]与真杆菌属密链群（Eubacteriumfissicatenagroup，ID: 14373）[OR = 1.20 (95%置信区间: 1.09, 1.33), p = 1.65×10^-4]分别与特应性皮炎和银屑病的发病风险升高相关。Dialister属则呈现负相关，提示其对特应性皮炎与玫瑰痤疮均具有保护作用。反向2SMR分析结果显示，上述炎症性皮肤病与所鉴定出的肠道菌群之间不存在反向因果关联。
研究结论：综上，本研究为肠道菌群与炎症性皮肤病之间的因果关联提供了证据支持。上述研究结果提示，补充特定细菌类群或可成为治疗特应性皮炎、银屑病及玫瑰痤疮的有效手段。