The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
Department of General Surgery, Devision of Dastroenterology and Pancreas, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
BMC Cancer. 2023 Nov 10;23(1):1091. doi: 10.1186/s12885-023-11493-y.
Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed.
In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study.
At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403-0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157-3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128-3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072-1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071-1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran's Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC.
Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.
肠道微生物群（GM）由大量多样的微生物组成，最近的研究强调了各种 GM 及其分泌代谢物在胰腺癌（PC）中的关键调节作用。然而，GM 与 PC 之间的因果关系尚未得到证实。
本研究采用两样本孟德尔随机化（MR）分析来探讨 GM 与 PC 之间的因果关系，以 MiBioGen 联盟的全基因组关联研究（GWAS）作为暴露因素，FinnGen 的 PC GWAS 数据作为结果因素。逆方差加权（IVW）是本研究的主要方法。
在属水平上，我们观察到 Senegalimassilia（OR：0.635，95%CI：0.403-0.998，P=0.049）对 PC 具有保护作用，而 Odoribacter（OR：1.899，95%CI：1.157-3.116，P=0.011）、Ruminiclostridium 9（OR：1.976，95%CI：1.128-3.461，P=0.017）、Ruminococcaceae（UCG011）（OR：1.433，95%CI：1.072-1.916，P=0.015）和 Streptococcus（OR：1.712，95%CI：1.071-1.736，P=0.025）被确定为 PC 的致病因素。此外，敏感性分析、Cochran's Q 检验、孟德尔随机化偏倚残差和异常值（MR-PRESSO）以及 MR-Egger 回归表明 GM 与 PC 之间不存在异质性、水平偏倚或反向因果关系。
我们的分析确立了特定 GM 与 PC 之间的因果关系，这可能为 GM 在 PC 中的潜在致病机制以及有效的治疗策略的制定提供新的见解。
