前瞻性研究早产儿出生后第4周的肠道菌群特征与1个月至6个月校正年龄(MCA)的神经发育之间的关系。2021年4月至2022年9月,从三家三级医院的三家NICU中招募了77名早产儿。在出生后第四周收集粪便样本。IlluminaMiSeq高通量测序技术用于检测肠道微生物群的组成和多样性。使用年龄和阶段问卷在1、3和6MCA进行早产儿的神经发育评估,第三版(ASQ-3)。斯皮尔曼相关性,广义线性混合模型(GLMM),和置换多变量方差分析(PERMANOVA)分析用于水平和前瞻性地探索每个时间点的肠道微生物和ASQ-3维度得分之间的关联。GLMM显示从1到6MCA的α多样性与神经发育轨迹之间没有显着关联。β多样性与1、3和6MCA的总运动得分显着相关(R2=0.067,p=0.001;R2=0.039,p=0.020;R2=0.031,p=0.047);3MCA的沟通得分(R2=0.030,p=0.040);6MCA的精细运动得分(R2=0.035,p=0.022)。在调整协变量后,GLMM显示,克雷伯菌的相对丰度与1至6MCA的粗大运动评分轨迹呈负相关(β=-1.449;95%CI,-2.275至-0.572;p=0.001),乳杆菌的相对丰度呈正相关(β=1.421;95%CI,0.139至2.702;p=0.030)。此外,链球菌的相对丰度与1~6MCA的精细运动轨迹呈负相关(β=-1.669;95%CI,-3.305~-0.033;p=0.046).
结论:我们的结果表明,新生儿肠道微生物多样性之间可能存在关联;克雷伯菌的相对丰度,链球菌,和乳酸杆菌;和神经发育从1到6MCA。在未来,临床工作人员可以关注肠道菌群定植的窗口期,并实施针对优势属的益生菌,以改善早产儿的神经发育。
背景:•在生物学和医学领域,目前的研究表明,肠道菌群可能通过肠-脑轴途径在神经发育的关键窗口期发挥重要作用。广泛的临床前研究暗示了最初的肠道定植在儿童长期神经发育中的重要作用。
背景:•在校正年龄(MCA)的6个月内,早期肠道菌群与早产儿的神经发育有关。
To prospectively investigate associations between the features of gut microbiota at the fourth week after birth in preterm infants and neurodevelopment from 1 month of corrected age to 6 months of corrected age (MCA). Seventy-seven preterm infants were recruited from three NICUs of three tertiary hospitals between Apr 2021 to Sep 2022. Stool samples were collected during the fourth week after birth. Illumina MiSeq high-throughput sequencing technology was used to detect the composition and diversity of gut microbiota. Neurodevelopment assessments of preterm infants were conducted at 1, 3, and 6 MCA using the Ages and Stages Questionnaire, the third edition (ASQ-3). Spearman correlation, a generalized linear mixed model (GLMM), and permutational multivariate analysis of variance (PERMANOVA) analysis were used to horizontally and prospectively explore the associations between gut microbial and ASQ-3 dimension scores at each time point. The GLMM showed no significant associations between the alpha diversity and neurodevelopmental trajectory from 1 to 6 MCA. The beta diversity was significantly associated with gross motor scores at 1, 3, and 6 MCA (R2 = 0.067, p = 0.001; R2 = 0.039, p = 0.020; R2 = 0.031, p = 0.047); communication scores at 3 MCA (R2 = 0.030, p = 0.040); and fine motor scores at 6 MCA (R2 = 0.035, p = 0.022). After adjusting for covariates, the GLMM showed that the relative abundance of Klebsiella was negatively associated with gross motor score trajectory from 1 to 6 MCA (β = - 1.449; 95% CI, - 2.275 to - 0.572; p = 0.001), while the relative abundance of Lactobacillus displayed a positive association (β = 1.421; 95% CI, 0.139 to 2.702; p = 0.030). Moreover, the relative abundance of Streptococcus was negatively associated with fine motor trajectory from 1 to 6 MCA (β = - 1.669; 95% CI, - 3.305 to - 0.033; p = 0.046).
CONCLUSIONS: Our results suggest a possible association between the neonatal gut microbial diversity; the relative abundance of Klebsiella, Streptococcus, and Lactobacillus; and neurodevelopment from 1 to 6 MCA. In the future, clinical staff can focus on the window period of gut microbiota colonization, and implement probiotics targeted at the dominant genera to improve the neurodevelopment of preterm infants.
BACKGROUND: • In the fields of biology and medicine, current studies suggest that gut microbiota may play an important role in the critical window period of neurodevelopment through the gut-brain axis pathway. • Extensive preclinical research has implied the vital role of the initial gut colonization in the long-term neurodevelopment of children.
BACKGROUND: • The early-life gut microbiota was associated with neurodevelopment in preterm infants within 6 months of corrected age (MCA).