Wang Yuqian, Cheng Tongfei, Cui Yifan, Qu Danyang, Peng Xin, Yang Liu, Xiao Xuwu
Department of Graduate, Dalian Medical University, Dalian, Liaoning, China.
Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Front Neurosci. 2024 Feb 14;18:1344125. doi: 10.3389/fnins.2024.1344125. eCollection 2024.
Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10) and genome-wide statistical significance threshold (5 × 10) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane's Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants.
肠道微生物群与早产儿不良神经发育结局相关；然而，确切的因果关系仍不清楚。在本研究中，我们进行了两样本孟德尔随机化（MR）分析，以全面研究肠道微生物群与早产儿不良神经发育结局之间的关系，并确定可能与早产儿不良神经发育结局的发生和发展相关的特定因果细菌。将MiBioGen生物群组的全基因组关联分析（GWAS）用作暴露数据。将来自芬兰基因组联盟R9的早产儿六种常见不良神经发育结局的GWAS用作结局数据。选择低于基因座全基因组显著性水平（1×10）和全基因组统计显著性阈值（5×10）的遗传变异，即单核苷酸多态性（SNP）作为工具变量（IV）。MR研究使用逆方差加权（IVW）作为主要方法。作为补充，我们还应用了另外三种MR方法：MR-Egger、加权中位数和加权模式。此外，使用Cochrane's Q检验、MR-Egger截距检验、孟德尔随机化多效性残差和异常值（MR-PRESSO）以及留一法进行敏感性分析。我们的研究表明特定肠道微生物群与早产儿神经发育结局之间存在因果关系。这些发现为肠道微生物群可能介导早产儿不良神经发育结局的机制提供了新的见解。
