PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, p = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, p = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, p = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, p = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, p = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, p = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, p = 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, p = 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, p = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, p = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, p = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, p = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, p = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, p = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, p = 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, p = 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.
UNASSIGNED: 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.
摘要：
■一些研究指出了肠道微生物群（GM）及其代谢产物在先天性巨结肠病（HSCR）发病机理中的关键作用。然而,GM和HSCR之间的详细因果关系仍然未知.
■在这项研究中，我们使用双样本孟德尔随机化（MR）分析来研究GM和HSCR之间的因果关系，基于MiBioGen联盟的全基因组关联研究（GWAS）和GWAS目录的HSCR数据。随后进行反向MR分析，和敏感性分析，Cochran的Q检验,MR多效性残差总和，异常值(MR-PRESSO)，MR-Egger截距用于分析异质性或水平多效性。开发16SrDNA测序和靶向质谱用于初步验证。
■在正向MR分析中，逆方差加权（IVW）估计表明Eggerthella（OR：2.66，95CI：1.23-5.74，p=0.01）是HSCR的危险因素，而肽球菌（OR：0.37，95CI：0.18-0.73，p=0.004），Ruminococus2（OR：0.32，95CI：0.11-0.91，p=0.03），梭菌1（OR：0.22，95CI：0.06-0.78，p=0.02），MollicutesRF9（OR：0.27，95CI：0.09-0.8，p=0.02），Ruminocycaceae（OR：0.16，95CI：0.04-0.66，p=0.01），和Paraprevotella（OR：0.45，95CI：0.21-0.98，p=0.04）是HSCR的保护因素，没有异质性或水平多效性。然而,反向MR分析显示，HSCR（OR：1.02，95CI：1-1.03，p=0.049）是Eggerthella的危险因素。此外，上述一些微生物群和短链脂肪酸（SCFA）在HSCR中发生了变化，显示出相关性。
■我们的分析建立了特定GM和HSCR之间的关系，确定特定细菌作为保护或危险因素。HSCR中重要的微生物群和SCFA发生了变化，强调进一步研究的重要性，并为发病机制和治疗提供新的见解。
■在这项研究中，我们使用双样本孟德尔随机化（MR）分析来研究GM和HSCR之间的因果关系，基于MiBioGen联盟的全基因组关联研究（GWAS）和GWAS目录的HSCR数据。随后进行反向MR分析，和敏感性分析，Cochran的Q检验,MR多效性残差总和，异常值(MR-PRESSO)，MR-Egger截距用于分析异质性或水平多效性。开发16SrDNA测序和靶向质谱用于初步验证。
■在正向MR分析中，逆方差加权（IVW）估计表明Eggerthella（OR：2.66，95CI：1.23-5.74，p=0.01）是HSCR的危险因素，而肽球菌（OR：0.37，95CI：0.18-0.73，p=0.004），Ruminococus2（OR：0.32，95CI：0.11-0.91，p=0.03），梭菌1（OR：0.22，95CI：0.06-0.78，p=0.02），MollicutesRF9（OR：0.27，95CI：0.09-0.8，p=0.02），Ruminocycaceae（OR：0.16，95CI：0.04-0.66，p=0.01），和Paraprevotella（OR：0.45，95CI：0.21-0.98，p=0.04）是HSCR的保护因素，没有异质性或水平多效性。然而,反向MR分析显示，HSCR（OR：1.02，95CI：1-1.03，p=0.049）是Eggerthella的危险因素。此外，上述一些微生物群和短链脂肪酸（SCFA）在HSCR中发生了变化，显示出相关性。
■我们的分析建立了特定GM和HSCR之间的关系，确定特定细菌作为保护或危险因素。HSCR中重要的微生物群和SCFA发生了变化，强调进一步研究的重要性，并为发病机制和治疗提供新的见解。
