DataSheet_1_Causal effects of gut microbiota on appendicitis: a two-sample Mendelian randomization study.pdf

BackgroundPrevious research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between appendicitis and the gut microbiota remains an unresolved and contentious issue.
MethodsIn this investigation, we performed a Mendelian randomization (MR) analysis employing publicly accessible summary data extracted from genome-wide association studies (GWAS) to elucidate the potential causal nexus between the gut microbiota and the development of appendicitis. We initially identified instrumental variables (IVs) through a comprehensive array of screening methodologies, subsequently executing MR analyses using the Inverse Variance Weighted (IVW) technique as our primary approach, supplemented by several alternative methods such as MR Egger, weighted median, simple mode, and weighted mode. Additionally, we implemented a series of sensitivity analysis procedures, encompassing Cochran’s Q test, MR-Egger intercept test, Mendelian Randomized Polymorphism Residual and Outlier (MR-PRESSO) test, and a leave-one-out test, to affirm the robustness and validity of our findings.
ResultsOur investigation indicates that an elevated prevalence of Deltaproteobacteria, Christensenellaceae, Desulfovibrionaceae, Eubacterium ruminantium group, Lachnospiraceae NK4A136 group, Methanobrevibacter, Desulfovibrionales, and Euryarchaeota is inversely associated with the risk of appendicitis. Conversely, we observed a positive correlation between an increased abundance of Family XIII, Howardella, and Veillonella and the susceptibility to appendicitis. Sensitivity analyses have corroborated the robustness of these findings, and Mendelian randomization analyses provided no indications of reverse causality.
ConclusionOur Mendelian randomization (MR) analysis has unveiled potential advantageous or detrimental causal associations between the gut microbiota and the occurrence of appendicitis. This study offers novel theoretical and empirical insights into the understanding of appendicitis pathogenesis, along with its implications for preventive and therapeutic strategies.

研究背景：既往研究已提出肠道菌群（gut microbiota）与阑尾炎发病之间存在潜在关联，但阑尾炎与肠道菌群间的确切因果关联仍未明确，且存在较大争议。
研究方法：本研究采用孟德尔随机化（Mendelian randomization, MR）分析方法，利用公开可得的全基因组关联研究（genome-wide association studies, GWAS）汇总数据，以阐明肠道菌群与阑尾炎发生之间的潜在因果关系。本研究首先通过一系列全面的筛选流程确定工具变量（instrumental variables, IVs），随后以逆方差加权（Inverse Variance Weighted, IVW）法作为核心分析手段，并辅以MR Egger、加权中位数法、简单众数法及加权众数法等多种替代分析方法。此外，本研究还实施了一系列敏感性分析，包括Cochran Q检验、MR-Egger截距检验、孟德尔随机化多态性残差与离群值（Mendelian Randomized Polymorphism Residual and Outlier, MR-PRESSO）检验以及留一法检验，以验证研究结果的稳健性与有效性。
研究结果：本研究发现，δ-变形菌纲（Deltaproteobacteria）、克里斯滕森菌科（Christensenellaceae）、脱硫弧菌科（Desulfovibrionaceae）、瘤胃真杆菌群（Eubacterium ruminantium group）、毛螺菌科（Lachnospiraceae）NK4A136群、产甲烷短杆菌属（Methanobrevibacter）、脱硫弧菌目（Desulfovibrionales）以及广古菌门（Euryarchaeota）的丰度升高与阑尾炎发病风险呈负相关。与之相反，XIII科（Family XIII）、Howardella属与韦荣球菌属（Veillonella）的丰度增加则与阑尾炎易感性呈正相关。敏感性分析证实了上述研究结果的稳健性，且孟德尔随机化分析未发现反向因果关系的相关迹象。
研究结论：本孟德尔随机化分析揭示了肠道菌群与阑尾炎发生之间潜在的有益或有害因果关联。本研究为阐明阑尾炎的发病机制提供了全新的理论与实证依据，同时也为其预防与治疗策略提供了新的思路。