Introduction: Early life is a critical window for the development of many bodily systems, including the gut microbiota and the central nervous system, that are interconnected through the gut-brain axis. These early life gut-brain axis connections are often studied through cross-sectional cohorts, limiting insights into temporal developmental trajectories. This longitudinal cohort study assessed whether gut microbial development over the first year of life is associated with socio-emotional development into childhood.

Methods: The PRIDE (pregnancy and infant development) BIOME study (n = 81, n = 42 males) is a focus cohort within the larger prospective PRIDE study. Gut microbiome was measured 5 times throughout the first year of life (at 2, 4, 6, 9, and 12 months through V4 16S rRNA sequencing) and socio-emotional development 8 times over 4.5 years, between 6 months and 5 years through the Ages and Stages Questionnaire: Social-Emotional (ASQ-SE). We related the development of the gut microbiota of infants throughout their first year of life with their socio-emotional development into childhood, the latter modeled as a slope per individual (ASQ slope). We assessed effects of time, ASQ slope and its interaction with time on microbial community measures alpha and beta diversity, as well as taxonomy, using linear mixed-effects models and PERMANOVA, correcting for sex, birth weight, gestational age, and sequencing depth.

Results: Expected developmental patterns on the gut microbiota over the first year of life were observed, including increased alpha diversity and clustering of beta diversity before and after solid food introduction. Interestingly, ASQ slope was a significant predictor of beta diversity (F(1,394) = 25.90, p = 0.001) and Bifidobacterium abundance across the first year of life (b = -0.745, SE = 0.24, pFDR = 0.023). Moreover, we observed a temporal association between ASQ slope and Eggerthella abundance (ASQ slope × timepoint interaction, b = 0.709, SE = 0.21, pFDR = 0.009). That is, Eggerthella abundance decreased across the group, but not in "late concern" infants, with concern about socio-emotional development at more recent timepoints.

Discussion: This study shows that genera Bifidobacterium and Eggerthella, known to be altered in mental health conditions such as autism spectrum disorder and depression, are already linked to socio-emotional development during early life. Hence, this work contributes to the identification of gut microbial candidates relevant for preventive screening of healthy gut-brain development and microbiota-targeted interventions.