He Rong-Chao, He Jun, Wang Hou-Dong, Shen Zhong
Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People's Republic of China.
Department of Colorectal Surgery, Hangzhou Third People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
Medicine (Baltimore). 2025 Aug 29;104(35):e44175. doi: 10.1097/MD.0000000000044175.
Perianal abscess and anal fistula are debilitating surgical conditions characterized by severe pain, persistent pus discharge, and prolonged recovery periods with high recurrence rates, collectively imposing profound burdens on patients' quality of life, social functioning, and work productivity. Research has indicated potential distinction regarding the composition of gut microbiota in patients suffering from perianal abscess and anal fistula. The causal effect is yet unclear. The MiBioGen consortium was utilized to acquire data pertaining to gut microbiota, while the outcome data was provided by another project called the MRC Integrative Epidemiology Unit Open Genome-wide Association Studies (IEU Open GWAS) project. We performed bidirectional two-sample Mendelian randomization (MR) using inverse variance weighted (IVW) as the primary method, selected for its robustness to balanced pleiotropy when valid instrumental variables are used. Additionally, sensitivity analyses were conducted to examine the robustness of the results. Four gut microbiota taxa showed causal associations with perianal abscess risk: Eubacterium brachy group (OR = 1.41, P = .004), Ruminococcaceae UCG003 (OR = 0.61, P = .007), Erysipelatoclostridium (OR = 0.68, P = .009), and Butyrivibrio (OR = 0.81, P = .016). For anal fistula, 8 taxa were significant: Catenibacterium (OR = 1.22, P = .042) and Eubacterium ruminantium group (OR = 1.17, P = .013) increased risk, while Haemophilus (OR = 0.79, P = .005), Alloprevotella (OR = 0.78, P = .001), Ruminiclostridium5 (OR = 0.79, P = .019), Erysipelotrichaceae UCG003 (OR = 0.82, P = .034), Butyrivibrio (OR = 0.88, P = .006), and Escherichia-Shigella (OR = 0.82, P = .039) conferred protection. Furthermore, the findings from the sensitivity analyses demonstrate robust stability in these conclusions. Reverse MR analyses did not suggest reverse causality. This is the first MR investigation into the causal relationships between the onset of perianal infections and particular taxa of the gut microbiota. It enhances our comprehension of the correlation.
肛周脓肿和肛瘘是使人虚弱的外科疾病，其特征为剧痛、持续流脓以及恢复期长且复发率高，给患者的生活质量、社交功能和工作效率带来了沉重负担。研究表明，肛周脓肿和肛瘘患者的肠道微生物群组成可能存在差异。但其因果关系尚不清楚。我们利用MiBioGen联盟获取与肠道微生物群相关的数据，而结果数据则由另一个名为医学研究委员会综合流行病学单位开放全基因组关联研究（IEU Open GWAS）项目提供。我们采用逆方差加权（IVW）作为主要方法进行双向双样本孟德尔随机化（MR）分析，选择该方法是因为在使用有效工具变量时，它对平衡多效性具有稳健性。此外，还进行了敏感性分析以检验结果的稳健性。四种肠道微生物分类群与肛周脓肿风险存在因果关联：短真杆菌属（Eubacterium brachy group，比值比[OR]=1.41，P=0.004）、瘤胃球菌科UCG003（Ruminococcaceae UCG003，OR=0.61，P=0.007）、丹毒丝菌属（Erysipelatoclostridium，OR=0.68，P=0.009）和丁酸弧菌属（Butyrivibrio，OR=0.81，P=0.016）。对于肛瘘，有8个分类群具有显著性：链状杆菌属（Catenibacterium，OR=1.22，P=0.042）和反刍真杆菌属（Eubacterium ruminantium group，OR=1.17，P=0.013）会增加风险，而嗜血杆菌属（Haemophilus，OR=0.79，P=0.005）、别普雷沃菌属（Alloprevotella，OR=0.78，P=0.001）、瘤胃梭菌5（Ruminiclostridium5，OR=0.79，P=0.019）、丹毒丝菌科UCG003（Erysipelotrichaceae UCG003，OR=0.82，P=0.034）和丁酸弧菌属（Butyrivibrio，OR=0.88，P=0.006）以及大肠埃希菌-志贺菌属（Escherichia-Shigella，OR=0.82，P=0.039）具有保护作用。此外，敏感性分析结果表明这些结论具有很强的稳定性。反向MR分析未显示反向因果关系。这是首次对肛周感染的发生与肠道微生物群特定分类群之间的因果关系进行MR研究。它增进了我们对这种相关性的理解。
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