Association between mid-childhood gut microbiome and neurocognitive outcomes in GESTE, a Canadian cohort Study

Abstract

BACKGROUND AND AIM: The microbiome is a dynamic ecosystem that may modulate neurodevelopment through the gut-brain axis. Altered microbial gut composition has been linked to childhood temperament and autism, however, to date, no studies estimate the association between the gut microbiome and neurocognitive function in a healthy mid-childhood population METHODS: Participants were 80 Caucasian children from the GESTation and the Environment, GESTE, a longitudinal birth cohort based in Sherbrooke, Canada. At the 6-8 years follow-up visit stool samples were analyzed with 16S rRNA sequencing. Intra-individual (alpha) microbiome diversity was computed using diversity (Shannon and Gini-Simpson) and dominance indices (Simpson and McNaughton’s). Inter-individual microbiome (beta) diversity was calculated using weighted and unweighted UniFrac, Bray-Curtis and Jaccard distances. Furthermore, bacterial phylum and family levels associations were examined. At the same follow-up visit, the children completed the WISC-IV (Wechsler Intelligence Scale for Children) questionnaire which includes seven subtests (block design, coding, total, forward and reverse digit span, information, and vocabulary). The associations between microbiome diversity, bacterial phyla and families and cognitive scores were assessed using generalized linear regression models adjusted for confounders, e.g., sociodemographic characteristics, breastfeeding and mode of delivery. Missing data points were imputed. The results were corrected using FDR method. RESULTS:Among the study cohort, 52% boys, 80% breastfed and 80% born vaginally with mean age, 6.5 years ± 0.5 at follow-up. Lower Shannon (β =-1.05, 95%CI: -1.71-0.39, p=0.02) and Gini-Simpson (β =1.04, 95%CI: -1.77-0.41, p=0.02) indices were associated with better long-term memory. No associations were observed for beta diversity. Higher total digit span was marginally associated with lower Desulfobacterota phylum abundance (β =-0.23, SE:0.09, p=0.09). CONCLUSIONS:Our findings suggest that while a healthier gut as measured by indices of microbial diversity was not associated with improved long-term memory, lower level of Desulfobacterota phylum bacterial taxa may be beneficial for the development of auditory working memory. KEYWORDS: Microbiome, Neurodevelopmental outcomes, Epidemiology.