Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, No. 2, Yongning North Road, Changzhou, 213003, Jiangsu Province, China.
Department of General Surgery, The Wujin Clinical college of Xuzhou Medical University, Changzhou, 213003, China.
BMC Gastroenterol. 2024 May 8;24(1):158. doi: 10.1186/s12876-024-03246-3.
Primary sclerosing cholangitis (PSC) is a complex disease with pathogenic mechanisms that remain to be elucidated. Previous observational studies with small sample sizes have reported associations between PSC, dyslipidemia, and gut microbiota dysbiosis. However, the causality of these associations is uncertain, and there has been no systematic analysis to date.
The datasets comprise data on PSC, 179 lipid species, and 412 gut microbiota species. PSC data (n = 14,890) were sourced from the International PSC Study Group, while the dataset pertaining to plasma lipidomics originated from a study involving 7174 Finnish individuals. Data on gut microbiota species were derived from the Dutch Microbiome Project study, which conducted a genome-wide association study involving 7738 participants. Furthermore, we employed a two-step Mendelian randomization (MR) analysis to quantify the proportion of the effect of gut microbiota-mediated lipidomics on PSC.
Following a rigorous screening process, our MR analysis revealed a causal relationship between higher levels of gene-predicted Phosphatidylcholine (O-16:1_18:1) (PC O-16:1_18:1) and an increased risk of developing PSC (inverse variance-weighted method, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.63). There is insufficient evidence to suggest that gene-predicted PSC impacts the levels of PC O-16:1_18:1 (OR 1.01, 95% CI 0.98-1.05). When incorporating gut microbiota data into the analysis, we found that Eubacterium rectale-mediated genetic prediction explains 17.59% of the variance in PC O-16:1_18:1 levels.
Our study revealed a causal association between PC O-16:1_18:1 levels and PSC, with a minor portion of the effect mediated by Eubacterium rectale. This study aims to further explore the pathogenesis of PSC and identify promising therapeutic targets. For patients with PSC who lack effective treatment options, the results are encouraging.
原发性硬化性胆管炎（PSC）是一种复杂的疾病，其发病机制尚待阐明。先前样本量较小的观察性研究报告了 PSC、血脂异常和肠道微生物群失调之间的关联。然而，这些关联的因果关系尚不确定，迄今为止尚无系统分析。
数据集包括 PSC、179 种脂质物种和 412 种肠道微生物物种的数据。PSC 数据（n=14890）来自国际 PSC 研究组，而血浆脂质组学数据集来自涉及 7174 名芬兰人的一项研究。肠道微生物物种的数据来自荷兰微生物组计划研究，该研究对 7738 名参与者进行了全基因组关联研究。此外，我们采用两步孟德尔随机化（MR）分析来量化肠道微生物群介导的脂质组学对 PSC 的影响比例。
经过严格的筛选过程，我们的 MR 分析表明，基因预测的磷脂酰胆碱（O-16:1_18:1）（PC O-16:1_18:1）水平升高与 PSC 发病风险增加之间存在因果关系（逆方差加权法，比值比（OR）1.30，95%置信区间（CI）1.03-1.63）。没有足够的证据表明基因预测的 PSC 会影响 PC O-16:1_18:1 的水平（OR 1.01，95%CI 0.98-1.05）。当将肠道微生物组数据纳入分析时，我们发现真杆菌属介导的遗传预测可以解释 PC O-16:1_18:1 水平变化的 17.59%。
本研究揭示了 PC O-16:1_18:1 水平与 PSC 之间存在因果关系，其中真杆菌属介导的作用占一小部分。本研究旨在进一步探索 PSC 的发病机制，并确定有前途的治疗靶点。对于缺乏有效治疗选择的 PSC 患者，结果令人鼓舞。
