Table_4_Premature Infant Gut Microbiome relationships with childhood behavioral scales: preliminary insights.xlsx

IntroductionVery Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants’ gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models.MethodsParents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin).ResultsNineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such as Veillonella dispar, Enterococcus, Escherichia coli, and Rumincococcus to later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years.DiscussionThese preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).

引言极度低出生体重（VLBW）婴儿，出生时体重不足1,500克，易患肠道菌群失调及后期神经心理发育障碍。行为效应虽与神经发育相关，但往往更为微妙且难以测量。此类微生物菌群失调所引起的后期神经行为后果的程度尚待确定。本研究探讨了婴儿肠道菌群与4岁早期儿童行为之间的关联，并通过多元分析结合线性模型识别了细菌类群。方法部分，家长完成了针对不同精神疾病诊断分类（DSM）的儿童行为量表（CBCL），包括情感、焦虑、广泛性发育、注意力缺陷/多动障碍和对抗性违抗等类别。所有CBCL得分在统计分析前均已根据性别、分娩方式、孕周、婴儿出生体重、败血症发生情况和抗生素使用天数进行了校正。为了确定早期生命肠道菌群与调整后的CBCL得分之间的关系，进行了典型相关分析（CCA）。通过线性模型的多变量分析（MaAsLin）测试了细菌扩增子序列变异（ASVs）与CBCL得分之间的关联。结果部分，本研究纳入了19名曾经出生体重极低并在新生儿重症监护室（NICU）住院的儿童。观察到早期生命中的肠道细菌，如Veillonella dispar、Enterococcus、Escherichia coli和Rumincococcus与4岁时的后期行为之间存在统计学上的显著关联。然而，未观察到早期生命肠道微生物群落的α多样性及4岁时的行为测量之间存在显著关联。讨论部分，这些初步的观察性数据为VLBW肠道菌群失调与儿童行为之间的关系提供了见解。本研究通过使用与精神疾病诊断与统计手册（DSM）相链接的标准工具，对不同的行为领域进行了分析，为肠道菌群分析的文献做出了贡献。