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早产儿脑白质损伤生命早期肠道菌群组成与临床指标的关联性分析

The association between gut microbiota composition and clinical indicators during early life in encephalopathy of prematurity
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摘要 目的分析早产儿脑病患儿出生后28 d内肠道菌群成分、多样性与临床指标之间的关系,筛选出对肠道菌群结构影响较大的临床指标。方法招募2022年4-12月广东医科大学附属医院出生胎龄<32周且体重<1.5 kg的早产儿。收集早产儿的胎粪(出生后24 h内)及出生后不同时间点(14和28 d)的粪便样本,进行16S rRNA基因测序。根据磁共振成像(MRI)检查结果,将患儿分为脑白质损伤组(WMI组,n=23)和非脑白质损伤组(nWMI组,n=48)。收集整理两组患儿临床资料,使用典范对应分析(CCA)来评估临床指标对肠道菌群结构的影响。采用Spearman对临床因素与肠道菌群组成进行相关性分析。结果基于单峰模型的CCA结果表明WMI分度、产前抗生素及剖宫产对WMI肠道菌群结构的影响较大。热图发现不动杆菌属、拟杆菌属、副拟杆菌属及葡萄球菌属与WMI分度成正相关(r=0.242、0.220、0.230、0.298,P均<0.05)。MaAsLin分析发现,肠球菌属与枕叶白质的表观弥散系数(ADC)成正相关(coefficient=0.736,P=0.004)。克雷伯菌属与侧脑室旁白质的ADC值也成正相关(coefficient=0.581,P=0.036),与侧脑室旁白质的各向异性分数(FA)值则成负相关(coefficient=-1.572,P=0.018)。肠道菌群的alpha多样性与内囊前肢白质发育密切相关。结论肠道菌群的成分、多样性与临床指标存在明显关联,WMI分度、产前抗生素、小于胎龄儿、枕叶白质及侧脑室旁白质弥散张力成像参数可被认为与WMI肠道菌群关联较大的临床指标。 Objective To examine the relationship between the composition and diversity of gut microbiota and clinical parameters in encephalopathy of prematurity,while also identifying crucial clinical indicators.Methods Preterm infants with a gestational age of less than 32 weeks and a birth weight of less than 1.5 kg were recruited for this study.Meconium samples were collected from these preterm infants within 24 hours after birth,as well as at different time points after birth(14 days and 28 days)for subsequent analysis using 16S rRNA gene sequencing.Based on the results of magnetic resonance imaging(MRI)examination,the subjects were categorized into two groups:white matter injury group(WMI group,n=23)and non-white matter injury group(nWMI group,n=48).Canonical corelation analysis(CCA)was employed to assess the impact of clinical indicators on gut microbiota structure,while Spearman correlation analysis was used to investigate the relationship between clinical factors and gut microbiota composition.Results The results of the CCA analysis revealed significant impacts of WMI grade,prenatal antibiotics,and cesarean section on the gut microbiota structure with WMI.The heatmap demonstrated positive correlations between Acinetobacter,Bacteroides,Parabacteroides and Staphylococcus and the severity of WMI(r=0.242,0.220,0.230,0.298;all P<0.05).MaAsLin analysis indicated a positive correlation between Enterococcus and apparent diffusion coefficient(ADC)values in occipital white matter(coefficient=0.736,P=0.004).Furthermore,Klebsiella exhibited a positive correlation with ADC values in periventricular white matter(coefficient=0.581,P=0.036)but showed a negative correlation with fraction anisotropy(FA)values in periventricular white matter(coeficient=-1.572,P=0.018).Additionally,it was observed that alpha diversity of gut microbiota closely relates to anterior limb development.Conclusions The composition and diversity of gut microbiota exhibited a significant correlation with clinical indicators,including the severity of WMI,prenatal antibiotics,small for gestational age status,as well as diffusion tensor imaging values related to occipital and periventricular white matter.These clinical indicators were closely associated with gut microbiota in WMI.
作者 刘玲 李烨姗 李承燕 蔡娜莉 敖当 林少珠 曾词正 LIU Ling;LI Yeshan;LI Chengyan;CAI Nali;AO Dang;LIN Shaozhu;ZENG Cizheng(Department of Paediatrics,Affiliated Hospital of Guangdong Medical University,Zhanjiang,Guangdong 524000,China)
出处 《热带医学杂志》 2025年第7期919-924,I0001,共7页 Journal of Tropical Medicine
基金 广东省医学科研基金(A2022441) 广东医科大学临床研究项目(LCYJ2020DL01,LCYJ2020B004)。
关键词 脑白质损伤 早产儿 肠道菌群 16S rRNA基因测序 各向异性分数 表观弥散系数 White matter injury Preterm infants Gut microbiota 16S rRNA gene sequencing Fraction anisotropy Apparent diffusion coefficient
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