Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Gastroenterology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, China.
Front Cell Infect Microbiol. 2024 Mar 15;14:1308742. doi: 10.3389/fcimb.2024.1308742. eCollection 2024.
BACKGROUND: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. METHODS: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. RESULTS: The outcomes derived from IVW substantiated that the presence of (OR = 0.44, = 0.034), (OR = 0.46, = 0.018), and (OR = 0.29, = 0.041) exerted a protective influence against BTC. Conversely, (OR = 2.21, = 0.017), (OR = 2.30, = 0.013), and (OR = 2.21, = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. CONCLUSION: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.
背景：越来越多的证据表明，肠道微生物组的组成与胆道癌（BTC）有关，但因果关系尚不清楚。本研究旨在探索肠道微生物群与 BTC 之间的因果关系，并评估肠道微生物组在促进 BTC 早期诊断中的效用。
方法：我们从日本生物银行（BBJ）数据库中获取了与 BTC 相关的全基因组关联研究（GWAS）的汇总数据（418 例病例和 159201 例对照）。此外，我们从 MiBioGen 联盟中获取了与肠道微生物组相关的 GWAS 汇总数据（N=18340）。分析主要采用逆方差加权（IVW）方法。通过使用多种统计技术，包括 Cochrane's Q 检验、MR-Egger 截距评估、MR-PRESSO 全局检验和逐个排除方法分析，对敏感性进行评估。最后，进行了反向孟德尔随机分析，以评估潜在的相互因果关系。
结果：IVW 的结果证实， （OR=0.44， =0.034）、 （OR=0.46， =0.018）和 （OR=0.29， =0.041）存在对 BTC 具有保护作用。相反， （OR=2.21， =0.017）、 （OR=2.30， =0.013）和 （OR=2.21， =0.017）与不利影响相关。为了评估任何反向因果效应，我们将 BTC 作为暴露因素，将肠道微生物组作为结果因素，分析结果表明 BTC 与五种不同类型的肠道微生物组之间存在关联。敏感性分析未发现异质性或多效性的实证指标。
结论：本研究首次通过 MR 方法鉴定了肠道微生物组与 BTC 风险之间存在有益或有害的因果关系的指示性数据。这些结果可能对制定针对 BTC 预防和生存改善的个体化治疗策略具有重要意义。
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