Feng Cuncheng, Gao Guanzhuang, Wu Kai, Weng Xiaoqi
Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Department of Gastrointestinal Surgery, Tongxiang First People's Hospital, Tongxiang, China.
Front Microbiol. 2024 Jul 17;15:1438778. doi: 10.3389/fmicb.2024.1438778. eCollection 2024.
Constipation is a prevalent gastrointestinal disorder affecting approximately 15% of the global population, leading to significant healthcare burdens. Emerging evidence suggests that gut microbiota plays a pivotal role in the pathogenesis of constipation, although causality remains uncertain due to potential confounding factors in observational studies. This study aims to clarify the causal relationships between gut microbiota and constipation using a bidirectional Mendelian Randomization (MR) approach, which helps to overcome confounding issues and reverse causality.
Utilizing data from genome-wide association studies (GWAS) from the MiBioGen consortium and other sources, we identified genetic variants as instrumental variables (IVs) for 196 bacterial traits and constipation. These IVs were rigorously selected based on their association with the traits and absence of linkage with confounding factors. We applied several MR methods, including Inverse Variance Weighted (IVW), MR Egger, and MR-PRESSO, to examine the causal effects in both directions.
Our analysis revealed a significant causal relationship where specific bacterial taxa such as (OR = 0.798, 95%CI: 0.711-0.896, < 0.001), (OR = 0.851, 95%CI: 0.740-0.979, = 0.024), (OR = 0.902, 95%CI: 0.817-0.996, = 0.041), r (OR = 0.823, 95%CI: 0.708-0.957, < 0.001), and , whereas others including (OR = 1.127, 95%CI: 1.008-1.261, = 0.036), (OR = 1.080, 95%CI: 1.018-1.145, = 0.025), (OR = 1.118, 95%CI: 1.014-1.233, = 0.002), and (OR = 1.274, 95%CI: 1.014-1.233, < 0.001) increase constipation risk. In the reverse MR analysis, constipation was found to influence the abundance of certain taxa, including , , , , , , , , and , indicating a bidirectional relationship. Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or horizontal pleiotropy.
The relationship between our study gut microbiota and constipation interacts at the genetic level, which gut microbiota can influence the onset of constipation, and constipation can alter the gut microbiota. , , , and play a protective role against constipation, while , , , and are associated with an increased risk. In addition, constipation correlates positively with the abundance of , and , while negatively with , , , , , and .
便秘是一种常见的胃肠道疾病，影响着全球约15%的人口，导致了巨大的医疗负担。新出现的证据表明，肠道微生物群在便秘的发病机制中起着关键作用，尽管由于观察性研究中存在潜在的混杂因素，因果关系仍不确定。本研究旨在使用双向孟德尔随机化（MR）方法阐明肠道微生物群与便秘之间的因果关系，该方法有助于克服混杂问题和反向因果关系。
利用来自MiBioGen联盟和其他来源的全基因组关联研究（GWAS）数据，我们确定了196种细菌特征和便秘的遗传变异作为工具变量（IVs）。这些IVs是根据它们与特征的关联以及与混杂因素无连锁关系而严格选择的。我们应用了几种MR方法，包括逆方差加权（IVW）、MR-Egger和MR-PRESSO，来检验两个方向上的因果效应。
我们的分析揭示了一种显著的因果关系，即特定的细菌类群如（比值比[OR]=0.798，95%置信区间[CI]：0.711-0.896，P<0.001）、（OR=0.851，95%CI：0.740-0.979，P=0.024）、（OR=0.902，95%CI：0.817-0.996，P=0.041）、r（OR=0.823，95%CI：0.708-0.957，P<0.001）以及其他类群，而包括（OR=1.127，95%CI：1.008-1.261，P=0.036）、（OR=1.080，95%CI：1.018-1.145，P=0.025）、（OR=1.118，95%CI：1.014-1.233，P=0.002）和（OR=1.274，95%CI：1.014-1.233，P<0.001）等其他类群会增加便秘风险。在反向MR分析中，发现便秘会影响某些类群的丰度，包括、、、、、、、、和，表明存在双向关系。敏感性分析证实了这些发现的稳健性，没有异质性或水平多效性的证据。
我们的研究表明肠道微生物群与便秘之间的关系在基因水平上相互作用，即肠道微生物群可影响便秘的发生，而便秘可改变肠道微生物群。、、、和对便秘起保护作用，而、、和与便秘风险增加有关。此外，便秘与、和的丰度呈正相关，而与、、、、和呈负相关。
