Longitudinal associations between early-life gut microbiome development and socioemotional behavior

Introduction

Established at birth by mainly maternal transfer and rapidly shaped in infancy by delivery mode, antibiotics, and diet, the gut microbiome is suggested to influence brain development and behaviour via immune, metabolic, and neuroendocrine pathways. However, prospective evidence linking microbiome development to later psychological outcomes in children remains limited. This study examines longitudinal associations between early-life gut microbiome and socioemotional outcomes across the first two years of life.

Methods

We used a subset of 645 healthy, full-term infants from the Finnish Health and Early Life Microbiota (HELMi) cohort (NCT03996304). Faecal samples from eight time points, from 3 weeks to 24 months, were analysed using 16S rRNA gene amplicon (V3–V4) sequencing to characterise gut bacterial community development. Socioemotional development across four domains was assessed using the Infant–Toddler Social and Emotional Assessment (ITSEA) questionnaire at a median age of 18.2 months (IQR 17.4–19.1), including four domains: internalising and externalising behaviour, dysregulation and competence. For statistical analysis, the multidimensionality of the genus-level community profile was reduced using unconstrained redundancy analysis (RDA) on centred log-ratio (CLR)-transformed relative abundances; the two most explanatory axes were retained. Longitudinal associations between microbiome diversity and richness, the axes RDA1 and RDA2, and ITSEA domains were tested using linear mixed-effects models, accounting for repeated measurements and adjusting for relevant covariates.

Results

Age-standardised internalising, externalising, and competence scores were not associated with alpha diversity at any time point. However, higher dysregulation scores were associated with lower Shannon diversity across all time points, reflecting a time-independent significant main effect (β = −0.029, SE = 0.014, t = −2.175, p = 0.030). Higher dysregulation was age-dependently negatively associated with RDA1 (age interaction: β = −0.0005, SE = 0.0001, t = −4.833, pFDR < 0.0001), with children showing a less mature community profile, characterised by higher relative abundance of e.g. Lacticaseibacillus, Enterobacter, and Clostridium sensu stricto 1 from 9 months onwards. Dysregulation was also associated with RDA2 (age interaction: β = 0.0006, SE = 0.0002, t = 2.503, pFDR = 0.031), indicating increasing divergence from typical microbiome composition towards communities loaded on e.g. Bifidobacterium, Ruminococcus gnavus group, and Escherichia–Shigella, particularly after 1 year of age. A one SD increase in externalising behaviour was associated with a 0.05-unit increase on RDA2 (β = 0.05, SE = 0.016, t = 3.236, pFDR = 0.003); however, this association tended to weaken with age (β = −0.0004, SE = 0.0002, t = −1.910, pFDR = 0.094).

Discussion and Conclusions

Among the four ITSEA domains, dysregulation showed the most consistent and developmentally dynamic associations with gut microbiome, being associated to altered microbiome composition especially towards toddlerhood, after 9 months of age. The dysregulation domain captures regulation of negative emotional states (reactivity and recovery), sleep and eating patterns, and sensory responsiveness that is heightened or atypical for age [1]. Traits, like sensory over-responsitivity, have been suggested as one of the bidirectional gut-brain axis mechanisms of interaction in autism spectrum disorder [2], but the direction of causality in current study remains elusive.

References

Carter, A.S., Briggs-Gowan, M.J., 2006. Infant–Toddler Social and Emotional Assessment (ITSEA) manual. Harcourt Assessment / The Psychological Corporation, San Antonio, TX.
Ringold, S.M., Cermak, S.A., Labus, J.S., Mayer, E.A., Aziz-Zadeh, L., 2026. Sensory Over-Responsivity in Autism: A Bidirectional Brain-Gut-Microbiome Model. Journal of Autism and Developmental Disorders. DOI: 10.1007/s10803-026-07279-3.