肠道微生物群与先天性巨结肠症之间的关联：一项双向两样本孟德尔随机化研究。
Association between gut microbiota and Hirschsprung disease: a bidirectional two-sample Mendelian randomization study.
作者信息
Liu Wei, Yan Hanlei, Jia Wanying, Huang Jingjing, Fu Zihao, Xu Wenyao, Yu Hui, Yang Weili, Pan Weikang, Zheng Baijun, Liu Yong, Chen Xinlin, Gao Ya, Tian Donghao
机构信息
Department of Pediatric Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
出版信息
Front Microbiol. 2024 Mar 7;15:1366181. doi: 10.3389/fmicb.2024.1366181. eCollection 2024.
BACKGROUND
Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.
METHODS
In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.
RESULTS
In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.
CONCLUSION
Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.
背景
多项研究指出肠道微生物群（GM）及其代谢产物在先天性巨结肠（HSCR）发病机制中起关键作用。然而，GM与HSCR之间的详细因果关系仍不清楚。
方法
在本研究中，我们基于微生物组全基因组关联研究（MiBioGen联盟）和全基因组关联研究目录（GWAS Catalog）中的HSCR数据，采用两样本孟德尔随机化（MR）分析来研究GM与HSCR之间的因果关系。随后进行了反向MR分析，并使用敏感性分析、 Cochr an's Q检验、MR多效性残差和离群值（MR-PRESSO）以及MR-Egger截距来分析异质性或水平多效性。开发了16S rDNA测序和靶向质谱用于初步验证。
结果
在前向MR分析中，逆方差加权（IVW）估计表明，迟缓埃格特菌（OR：2.66，95%CI：1.23-5.74，P = 0.01）是HSCR的危险因素，而消化球菌（OR：0.37，95%CI：0.18-0.73，P = 0.004）、瘤胃球菌2（OR：0.32，95%CI：0.11-0.91，P = 0.03）、梭菌科1（OR：0.22，95%CI：0.06-0.78，P = 0.02）、柔膜菌纲RF9（OR：0.27，95%CI：0.09-0.8，P = 0.02）、瘤胃球菌科（OR：0.16，95%CI：0.04-0.66，P = 0.01）和副普雷沃菌属（OR：0.45，95%CI：0.21-0.98，P = 0.04）是HSCR的保护因素，且不存在异质性或水平多效性。然而，反向MR分析表明，HSCR（OR：1.02，95%CI：1-1.03，P = 0.049）是迟缓埃格特菌的危险因素。此外，上述一些微生物群和短链脂肪酸（SCFAs）在HSCR中发生了改变，显示出相关性。
结论
我们的分析确定了特定GM与HSCR之间的关系，确定了特定细菌为保护因素或危险因素。HSCR中重要的微生物群和SCFAs发生了改变，强调了进一步研究的重要性，并为发病机制和治疗提供了新的见解。
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