极早产儿肠道菌群分布对纠正年龄2周岁时神经心理发育影响探讨

Impact of gut microbiota composition on neuropsychological development of very preterm infants at corrected age of 2 years

摘要

目的 探讨极早产儿（胎龄28～32⁺⁶周）肠道菌群分布对纠正年龄2周岁时神经心理发育的影响。方法 选择2023年1月1日至2023年12月31日福建医科大学附属三明第一医院新生儿重症监护病房因各种原因收治住院的极早产儿31例。根据发育商测评值分为神经发育正常组20例和神经发育迟缓组11例。极早产儿纠正年龄2周岁时采用智能儿童发育测查系统（0～6岁儿童发育行为评估量表）进行评价，发育商≥85分为正常，1个及以上能区测评值<85分时判定为发育迟缓；使用16S rRNA测序，检测婴儿肠道菌群结构和多样性，并分析生命早期肠道菌群与神经心理发育得分的关系。结果 神经心理发育正常组出生24 h内肠道菌群放线菌门的相对丰度高于神经心理发育迟缓组，差异有统计学意义(P<0.001)，拟杆菌门的丰度低于神经心理发育迟缓组(P<0.001); 两组间Alpha多样性比较差异无统计学意义（P&gt;0.05）。Spearman's相关性分析显示出生后24 h内早产儿肠道中的双歧杆菌属相对丰度与纠正年龄2周岁时精细动作及语言发育能区得分呈正相关，而葡萄球菌属的相对丰度与精细动作及社交行为发育能区得分呈负相关。结论 早产儿的生命早期肠道菌群构成存在差异，这种差异与早产儿神经发育水平相关联。

Abstract

Objective To investigate the influence of gut microbiota composition on neuropsychological development of very preterm infants(gestational age 28–32⁺⁶ weeks) at a corrected age of 2 years. Methods Totally 31 very preterm infants were chosen, who were admitted for various reasons to NICU of Affiliated Sanming First Hospital of Fujian Medical University from Jan. 1, 2023 to Dec. 31, 2023. Based on the scores of developmental quotient assessment, they were divided into two groups: 20 in the normal neurodevelopment group and 11 in the delayed neurodevelopment group. At the corrected age of 2 years, neuropsychological development was assessed using the Intelligent Child Development Examination System(developmental scale for children aged 0-6 years). A developmental quotient(DQ) score of ≥85 was considered normal, while a score below 85 in one or more domains indicated developmental delay. The structure and diversity of the infant gut microbiota were analyzed using 16S rRNA sequencing, and the relationship between early-life gut microbiota and neuropsychological development scores was analyzed. Results The relative abundance of Actinobacteria within 24 hours after birth was higher in the normal neurodevelopment group than in the delayed group(P<0.001), while the abundance of Bacteroidetes was lower(P<0.001). No significant difference in alpha diversity was observed between the two groups(P&gt;0.05). Spearman's correlation analysis revealed a positive correlation between the relative abundance of Bifidobacterium in the intestines within the first 24 hours after birth and scores in fine motor and language development domains at the corrected age of 2 years. In contrast, the relative abundance of Staphylococcus was negatively correlated with scores in fine motor and social behavior development domains. Conclusion Early-life gut microbiota composition differs in very preterm infants, and the difference is associated with their neurodevelopmental levels.

关键词

极早产儿 / 肠道菌群 / 年龄 / 神经心理 / 发育

Key words

Very preterm infant / Gut microbiota / Age / Neuropsychological / Development

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基金资助

福建省自然科学基金项目（面上）(2023J011752)