Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
Department of Thyroid and Breast Surgery III, Cangzhou Central Hospital, Cangzhou, China.
Medicine (Baltimore). 2024 Sep 27;103(39):e39852. doi: 10.1097/MD.0000000000039852.
This Mendelian randomization (MR) study aims to explore the relationship between gut microbiota and the occurrence of cholelithiasis, as well as the impact of cholecystectomy on the gut microbiota. This study leverages data on exposures and outcomes from the GWAS database, employing the inverse variance weighting (IVW) method to obtain primary causal estimates. Heterogeneity is assessed using Cochran Q and Rücker Q tests through both IVW and MR-Egger methods. Pleiotropy is evaluated using the Egger-intercept method, while sensitivity analyses are conducted via leave-one-out tests. Additionally, the F-statistic is calculated to assess the presence of weak instrument bias. Finally, the MR-PRESSO method is utilized to validate the findings concerning the relationship between gut microbiota and the incidence of cholelithiasis, as well as the impact of cholecystectomy on gut microbiota composition. The genera Butyricicoccus (ID: 2055), Solibacillus (ID: 11348), Anaerotruncus (ID: 2054), Allisonella (ID: 2174), and Howardella (ID: 2000) have been found to decrease the genetically predicted probability of cholelithiasis. Reverse MR analysis indicates that the occurrence of cholelithiasis reduces the levels of gut microbiota such as Blautia (ID: 1992), Anaerofilum (ID: 2053), Howardella (ID: 2000), Butyricicoccus (ID: 2055), Solibacillus (ID: 11348), Allisonella (ID: 2174), Anaerotruncus (ID: 2054), and Firmicutes (ID: 1672). Additionally, the genera Odoribacter (ID: 952), and Holdemanella (ID: 2157) increase the genetically predicted risk of cholecystectomy. Reverse MR results show that post-cholecystectomy reduces the levels of gut microbiota such as Blautia (ID: 1992), Butyricicoccus (ID: 2055), Alistipes (ID: 11296), Oxalobacteraceae (ID: 2966), and Ruminococcaceae UCG010 (ID: 11367). Conversely, post-cholecystectomy increases the levels of gut microbiota such as Odoribacter (ID: 952), an unknown family (ID: 1000001214), an unknown genus (ID: 1000001215), Aeromonadales (ID: 1591), Holdemanella (ID: 2157), Phascolarctobacteria (ID: 1589), and Eggerthella (ID: 819). All study results show no horizontal pleiotropy, and the MR-PRESSO validation results are consistent with the MR analysis findings. This study elucidates the relationship between gut microbiota and the occurrence of cholelithiasis, as well as the impact of cholecystectomy on the gut microbiota. These findings have clinical significance for diagnosing disease onset and understanding digestive function changes following gallbladder removal, providing theoretical support for further investigation into the molecular mechanisms underlying cholelithiasis.
本孟德尔随机化（MR）研究旨在探索肠道微生物群与胆石病发生之间的关系，以及胆囊切除术对肠道微生物群的影响。本研究利用 GWAS 数据库中的暴露和结局数据，采用逆方差加权（IVW）方法获得主要因果估计。使用 Cochran Q 和 Rücker Q 检验通过 IVW 和 MR-Egger 方法评估异质性。使用 Egger 截距法评估多效性，通过逐个删除进行敏感性分析。此外，计算 F 统计量以评估弱工具偏倚的存在。最后，使用 MR-PRESSO 方法验证肠道微生物群与胆石病发生之间的关系以及胆囊切除术对肠道微生物群组成的影响的研究结果。发现以下属降低了胆石病的遗传预测概率：Butyricicoccus（ID：2055）、Solibacillus（ID：11348）、Anaerotruncus（ID：2054）、Allisonella（ID：2174）和 Howardella（ID：2000）。反向 MR 分析表明，胆石病的发生降低了肠道微生物群的水平，如 Blautia（ID：1992）、Anaerofilum（ID：2053）、Howardella（ID：2000）、Butyricicoccus（ID：2055）、Solibacillus（ID：11348）、Allisonella（ID：2174）、Anaerotruncus（ID：2054）和 Firmicutes（ID：1672）。此外，Odoribacter（ID：952）和 Holdemanella（ID：2157）属增加了胆囊切除术的遗传预测风险。反向 MR 结果表明，胆囊切除术后肠道微生物群的水平降低，如 Blautia（ID：1992）、Butyricicoccus（ID：2055）、Alistipes（ID：11296）、Oxalobacteraceae（ID：2966）和 Ruminococcaceae UCG010（ID：11367）。相反，胆囊切除术后肠道微生物群的水平增加，如 Odoribacter（ID：952）、一个未知科（ID：1000001214）、一个未知属（ID：1000001215）、Aeromonadales（ID：1591）、Holdemanella（ID：2157）、Phascolarctobacteria（ID：1589）和 Eggerthella（ID：819）。所有研究结果均未显示水平多效性，MR-PRESSO 验证结果与 MR 分析结果一致。本研究阐明了肠道微生物群与胆石病发生之间的关系，以及胆囊切除术对肠道微生物群的影响。这些发现对诊断疾病发作和理解胆囊切除术后消化功能变化具有临床意义，为进一步研究胆石病的分子机制提供了理论支持。
