Development of the gut microbiota in healthy children in the first ten years of life: associations with internalizing and externalizing behavior

BACKGROUND: Increasing evidence indicates that psychopathological disorders are associated with the gut microbiota. However, data are largely lacking from long-term longitudinal birth cohorts, especially those comprising low-risk healthy individuals. Therefore, this study aims to describe gut microbiota development in healthy children from birth till age 10 years, as well as to investigate potential associations with internalizing and externalizing behavior. RESULTS: Fecal microbial composition of participants in an ongoing longitudinal study (N = 193) was analyzed at 1, 3 and 4 months, and 6 and 10 years of age by 16S ribosomal RNA gene sequencing. Based on these data, three clusters were identified in infancy, two of which were predominated by Bifidobacterium. In childhood, four clusters were observed, two of which increased in prevalence with age. One of the childhood clusters, similar to an enterotype, was highly enriched in genus-level taxon Prevotella_9. Breastfeeding had marked associations with microbiota composition up till age 10, implying an extended role in shaping gut microbial ecology. Microbial clusters were not associated with behavior. However, Prevotella_9 in childhood was positively related to mother-reported externalizing behavior at age 10; this was validated in child reports. CONCLUSIONS: This study validated previous findings on Bifidobacterium-enriched and -depleted clusters in infancy. Importantly, it also mapped continued development of gut microbiota in middle childhood. Novel associations between gut microbial composition in the first 10 years of life (especially Prevotella_9), and externalizing behavior at age 10 were found. Replications in other cohorts, as well as follow-up assessments, will help determine the significance of these findings.