PDF(Pubmed)
Abstract：
BACKGROUND: The gut microbiota is recognized as a regulator of brain development and behavioral outcomes during childhood. Nonetheless, associations between the gut microbiota and behavior are often inconsistent among studies in humans, perhaps because many host-microbe relationships vary widely between individuals. This study aims to stratify children based on their gut microbiota composition (i.e., clusters) and to identify novel gut microbiome cluster-specific associations between the stool metabolomic pathways and child behavioral outcomes.
METHODS: Stool samples were collected from a community sample of 248 typically developing children (3-5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated.
RESULTS: Four different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner.
CONCLUSIONS: These data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract.
METHODS: Stool samples were collected from a community sample of 248 typically developing children (3-5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated.
RESULTS: Four different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner.
CONCLUSIONS: These data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract.
摘要：
背景：肠道微生物群被认为是儿童期大脑发育和行为结果的调节因子。尽管如此，在人类研究中，肠道微生物群和行为之间的关联通常不一致，也许是因为许多宿主-微生物关系在个体之间差异很大。这项研究旨在根据儿童的肠道微生物组成对其进行分层(即，集群)，并确定粪便代谢组学途径和儿童行为结果之间的新型肠道微生物组集群特异性关联。
方法：从248名典型发育儿童（3-5岁）的社区样本中收集粪便样本。使用16S测序分析肠道微生物群,而LC-MS/MS用于非靶向代谢组学。父母报告的行为结果(即，适应性技能,内部化,Externalizing,行为症状,发展性社交障碍）使用儿童行为评估系统（BASC-2）进行评估。使用Dirichlet多项方法，根据儿童的肠道菌群组成对儿童进行分组，之后，研究了代谢组和行为结局的差异。
结果：确定了四种不同的肠道微生物群，其中富含拟杆菌和双歧杆菌（Ba2）的簇具有最明显的粪便代谢组。以双歧杆菌丰度高(Bif)为特征的集群，以及簇Ba2，与较低的自适应技能得分及其子组成部分社会技能有关。簇Ba2也具有显著较低的粪便组氨酸对尿犬酸盐的更新，这反过来又以集群依赖的方式与较低的社会技能得分相关。最后,簇Ba2参与半乳糖代谢的化合物水平增加(即，水苏糖,棉子糖,α-D-葡萄糖)，其中α-D-葡萄糖与自适应技能亚组分日常生活得分(即，以依赖于集群的方式执行基本日常任务的能力)。
结论：这些数据显示了肠道菌群之间的新关联，它的代谢物，以及通常发育中的学龄前儿童的行为结果。我们的结果支持以下概念：基于集群的分组可用于开发更个性化的干预措施以支持儿童行为结果。视频摘要。
方法：从248名典型发育儿童（3-5岁）的社区样本中收集粪便样本。使用16S测序分析肠道微生物群,而LC-MS/MS用于非靶向代谢组学。父母报告的行为结果(即，适应性技能,内部化,Externalizing,行为症状,发展性社交障碍）使用儿童行为评估系统（BASC-2）进行评估。使用Dirichlet多项方法，根据儿童的肠道菌群组成对儿童进行分组，之后，研究了代谢组和行为结局的差异。
结果：确定了四种不同的肠道微生物群，其中富含拟杆菌和双歧杆菌（Ba2）的簇具有最明显的粪便代谢组。以双歧杆菌丰度高(Bif)为特征的集群，以及簇Ba2，与较低的自适应技能得分及其子组成部分社会技能有关。簇Ba2也具有显著较低的粪便组氨酸对尿犬酸盐的更新，这反过来又以集群依赖的方式与较低的社会技能得分相关。最后,簇Ba2参与半乳糖代谢的化合物水平增加(即，水苏糖,棉子糖,α-D-葡萄糖)，其中α-D-葡萄糖与自适应技能亚组分日常生活得分(即，以依赖于集群的方式执行基本日常任务的能力)。
结论：这些数据显示了肠道菌群之间的新关联，它的代谢物，以及通常发育中的学龄前儿童的行为结果。我们的结果支持以下概念：基于集群的分组可用于开发更个性化的干预措施以支持儿童行为结果。视频摘要。
