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The human gut microbiota (GM) develops into adult-like composition around 3 to 5 years of age (Stewart et al., 2018). Thus, the first five years of life represent a sensitive period in gut microbiome formation. Similarly, humans show remarkable cognitive development, especially the aspect of executive function (EF) in this period (Kerr and Zelazo, 2004). EF can be defined as the goal-directed cognitive process comprising explicit emotion regulation (EER), i.e., control over one’s emotional state, and cognitive control (CC), controlling thoughts and actions in emotionally neutral situations (Zelazo, 2002). A recent study has shown that gut microbes relate to brain functions of emotional processing in infancy (e.g., Gao et al., 2019). Based on these, we hypothesized that preschool children having difficulty in EER may have GM characteristics distinct from those of controls.
We recruited 257 Japanese children between 3 and 4 years of age and measured their EER using an inhibitory self-control index on the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) questionnaire (Ukena et al, 2006; Gioia et al, 2003). Of these, 26 were allocated to the EER-risk group (Mage 46.0 ± 6.3 months) and 231 to the EER-control group (Mage 46.6 ± 6.3 months) based on the BRIEF-P cutoff value. Using BRIEF-P's Emergent Metacognition Index we also set up a CC-risk group (N = 20, Mage 45.6 ± 6.4 months) and CC-control group (N = 237, Mage 46.6 ± 6.3 months). GM was evaluated using 16S ribosomal RNA gene sequencing and subsequently compared. In addition, we examined the dietary habits and physical symptoms of the recruits.
Analysis of compositions of microbiomes with bias correction revealed significant differences in the GM profiles of the EER-risk and EER-control group. The EER-risk group had a significantly higher abundance of Actinomyces and Sutterella than in the control group (false discovery rate [FDR]-adjusted p < 0.10). Furthermore, the abundance of Lachnospira and Monoglobus were lower in the EER-risk group than in the control group (p < 0.05), but these differences were not statistically significant after p-value adjustment (FDR-adjusted p = 0.65). In addition, the EER-risk individuals had a significantly lower consumption frequency of green/yellow vegetables and significantly higher incidence of pet allergy than that in the EER-control group (FDR-adjusted p < 0.05). Importantly, no significant difference was found between the CC-risk and CC-control groups.
The GM of young children with the EER-risk contained more intestinal inflammation-related bacteria (i.e., Actinomyces and Sutterella) and less short-chain fatty acids (SCFA)-producing bacteria (i.e., Lachnospira and Monoglobus), indicating a disruption of intestinal homeostasis. Furthermore, we found a possible increased incidence of inflammation-related diseases in the EER-risk individuals. These GM differences were not observed in the CC-risk children. The findings of the current study suggest that individual differences in gut microbiota development during early childhood could be more related to executive functions in aspects of emotional processing rather than that of cognitive aspects.