Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China.
Institute of Basic Research in Clinical Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Front Immunol. 2022 Jul 4;13:921546. doi: 10.3389/fimmu.2022.921546. eCollection 2022.
Intestinal dysbiosis is associated with inflammatory bowel disease (IBD). Ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD, are characterized by unique microbial signatures, respectively. However, it is unclear whether UC or CD has a specific causal relationship with gut microbiota.
To investigate the potential causal associations between gut microbial genera and IBD, UC, or CD, two-sample Mendelian randomization (MR) analyses were conducted.
We obtained genome-wide association study (GWAS) summary statistics of gut microbiota and IBD, UC, or CD from published GWASs. Two-sample MR analyses were performed to identify potential causal gut microbial genera for IBD, UC, and CD using the inverse-variance weighted (IVW) method. Sensitivity analyses were also conducted to validate the robustness of the primary results of the MR analyses. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.
Combining the results from the primary and sensitivity analyses, six bacterial genera were associated with the risk of IBD, UC, or CD in the IVW method. Briefly, group was associated with a lower risk of IBD (=0.011) and UC (=1.00×10), whereas 2 was associated with a higher risk of IBD (=0.022) and UC (=0.007). In addition, we found a positive association between with IBD (=0.001) and CD (=0.002), and UCG014 with IBD (=0.005) and CD (=0.007). We also noticed a negative association between (=0.044) and IBD, and between UCG001 (=0.023) and CD. We did not find causal effects of IBD, UC, or CD on these bacterial genera in the reverse MR analysis.
This study expanded gut microbial genera that were causally associated with the risk of IBD, and also revealed specificity-gut microbial genera for UC or CD.
肠道菌群失调与炎症性肠病（IBD）有关。溃疡性结肠炎（UC）和克罗恩病（CD）是 IBD 的两种亚型，分别具有独特的微生物特征。然而，UC 或 CD 是否与肠道微生物群有特定的因果关系尚不清楚。
采用两样本 Mendelian 随机化（MR）分析，研究肠道微生物属与 IBD、UC 或 CD 的潜在因果关系。
我们从已发表的 GWAS 中获得了肠道微生物群和 IBD、UC 或 CD 的全基因组关联研究（GWAS）汇总统计数据。采用逆方差加权（IVW）法，进行两样本 MR 分析，以确定与 IBD、UC 和 CD 相关的潜在因果肠道微生物属。还进行了敏感性分析，以验证 MR 分析的主要结果的稳健性。最后，进行了反向 MR 分析，以评估反向因果关系的可能性。
结合主要和敏感性分析的结果，在 IVW 方法中，有 6 个细菌属与 IBD、UC 或 CD 的发病风险相关。具体而言，属与 IBD（=0.011）和 UC（=1.00×10）的风险降低有关，而属与 IBD（=0.022）和 UC（=0.007）的风险增加有关。此外，我们发现与 IBD（=0.001）和 CD（=0.002）呈正相关，与 IBD（=0.005）和 CD（=0.007）呈正相关。我们还注意到与 IBD（=0.044）和 CD（=0.023）呈负相关。在反向 MR 分析中，我们没有发现 IBD、UC 或 CD 对这些细菌属有因果影响。
本研究扩展了与 IBD 风险有因果关系的肠道微生物属，并揭示了 UC 或 CD 特异性的肠道微生物属。
