Gut Microbiota Development In Healthy Children In The First Decade Of Life: Associations With Behavior

• In Event: Poster Session 03
  In Poster Session: PS 03 Topic - Biological Processes: Psychophysiology

Abstract

Background: Increasing evidence indicates that psychopathological disorders in adulthood such as depression, anxiety, and schizophrenia are associated with the gut microbiota. The microbes in our gut, mostly consisting of bacteria, would influence the brain through the bidirectional microbiota-gut-brain axis communications. Studies in animal models show that the gut microbiota also influence brain and behavioral development. Emerging studies in human children, many cross-sectional and in infancy, are starting to show links between the gut bacteria and child behavior. To our knowledge, the present study is the first to longitudinally investigate the gut microbiota development in a relatively large group of children from birth to age 10. The goals are twofold: to describe normative development of the gut microbiota throughout this lengthy period and to investigate potential associations of the gut microbiota with measures of internalizing and externalizing behavior in middle childhood.

Methods: Participants (N=193) belong to an ongoing longitudinal study on a healthy cohort. Gut microbial compositions were analyzed at 1, 3, 4 months of age, and 6 and 10 years of age by 16S rRNA sequencing. Bacterial clusters were identified by Dirichlet Multinomial Mixtures in infancy and childhood, respectively. Internalizing and externalizing behavior was measured in childhood with the Child Behavior Checklist (age 6; mothers) and Strengths and Difficulties Questionnaire (age 10; mothers and children). Associations of the measures of behavior with the gut microbiota were determined by Redundancy Analysis and Multilevel Modelling.

Results: Based on differences in microbial community structure, 3 bacterial clusters were identified in infancy, and 4 were identified in childhood (Fig.1). Infancy_1 and Infancy_2 clusters, dominated by Bifidobacterium (Fig.2), showed a significantly higher proportion of vaginal deliveries than Infancy_3. As for clusters in childhood, Childhood_2, similar to an adult enterotype, was characterized with the highest abundance of Prevotella_9. During infancy, many individuals transitioned to Infancy_2. In childhood, children tended to end up at Childhood_3 and Childhood_4. Additionally, breastfeeding, known to date only as a prominent determinant of gut microbiota in infancy, was remarkably also independently associated with microbial compositions at ages 6 and 10. With respect to our second goal of relating bacteria to behavior, no consistent differences in behavior were observed between bacterial clusters. However, microbial compositions in both infancy and childhood were significantly associated with mother-reported externalizing behavior at age 10. Particularly, Prevotella_9 in childhood was positively related to increased mother-reported externalizing behavior at age 10; this was further validated in child reports at the same age.

Conclusions: This study validates previous findings on Bifidobacterium enriched and reduced clusters in infancy. Importantly, we show that the gut microbiota continues to develop into middle childhood showing characteristics of adult microbiota. This is well beyond the age of 2-3 years, when the gut microbiota was previously thought to become relatively stable. Additionally, we found novel associations between gut microbial compositions in the first 10 years of life (especially Prevotella_9), and externalizing behavior at age 10. Replications in other community cohorts as well as further follow-ups at later ages will help determine the significance of these findings.

Authors

• Yangwenshan Ou, Wageningen University and Research
  Presenting Author

• Clara Belzer, Wageningen University & Research
  Non-Presenting Author

• Hauke Smidt, Wageningen University & Research
  Non-Presenting Author

• Carolina de Weerth, Radboud University Medical Center
  Non-Presenting Author