Gut microbiota and MR results for ACNE.

BackgroundIncreasing evidence suggests that alterations in gut microbiota are associated with a variety of skin diseases. However, whether this association reflects a causal relationship remains unknown. We aimed to reveal the causal relationship between gut microbiota and skin diseases, including psoriasis, atopic dermatitis, acne, and lichen planus.MethodsWe obtained full genetic association summary data for gut microbiota, psoriasis, atopic dermatitis, acne, and lichen planus from public databases and used three methods, mainly inverse variance weighting, to analyze the causal relationships between gut microbiota and these skin diseases using bidirectional Mendelian randomization, as well as sensitivity and stability analysis of the results using multiple methods.ResultsThe results showed that there were five associated genera in the psoriasis group, seven associated genera were obtained in the atopic dermatitis group, a total of ten associated genera in the acne group, and four associated genera in the lichen planus group. The results corrected for false discovery rate showed that Eubacteriumfissicatenagroup (P = 2.20E-04, OR = 1.24, 95%CI:1.11–1.40) and psoriasis still showed a causal relationship. In contrast, in the reverse Mendelian randomization results, there was no evidence of an association between these skin diseases and gut microbiota.ConclusionWe demonstrated a causal relationship between gut microbiota and immune skin diseases and provide a new therapeutic perspective for the study of immune diseases: targeted modulation of dysregulation of specific bacterial taxa to prevent and treat psoriasis, atopic dermatitis, acne, and lichen planus.**研究背景**：越来越多的证据表明，肠道菌群（gut microbiota）的改变与多种皮肤疾病存在关联。然而，此类关联是否代表因果关系仍不明确。本研究旨在阐明肠道菌群与银屑病（psoriasis）、特应性皮炎（atopic dermatitis）、痤疮（acne）及扁平苔藓（lichen planus）等皮肤疾病之间的因果关系。 **研究方法**：我们从公共数据库中获取了肠道菌群、银屑病、特应性皮炎、痤疮及扁平苔藓的全基因关联汇总数据；采用以逆方差加权法（inverse variance weighting）为主的三种分析方法，通过双向孟德尔随机化（bidirectional Mendelian randomization）分析肠道菌群与上述皮肤疾病的因果关系，并通过多种方法对分析结果开展敏感性与稳定性验证。 **研究结果**：分析结果显示，银屑病组共筛选出5个关联菌属，特应性皮炎组得到7个关联菌属，痤疮组共计10个关联菌属，扁平苔藓组则有4个关联菌属。经错误发现率（false discovery rate）校正后的结果表明，真杆菌属群（Eubacteriumfissicatenagroup）（P=2.20×10⁻⁴，比值比（OR, odds ratio）=1.24，95%置信区间（CI, confidence interval）：1.11~1.40）与银屑病仍存在显著因果关联。与之相反，反向孟德尔随机化（reverse Mendelian randomization）分析结果未发现上述皮肤疾病与肠道菌群之间存在关联的证据。 **研究结论**：本研究证实了肠道菌群与免疫相关性皮肤疾病之间存在因果关系，为免疫性疾病的研究提供了全新的治疗视角：通过靶向调控特定细菌类群的失调状态，以预防和治疗银屑病、特应性皮炎、痤疮及扁平苔藓。