Microbiome-behavior coupling shapes infant adaptation to early maternal unpredictability

How do some human infants adapt to environmental challenges while others do not? We examined whether infant behavioral responses to maternal unpredictability predict early inhibitory control and are linked to gut microbial community composition and neuroactive metabolic potential. Maternal unpredictability, quantified as the entropy of sensory signal transitions during mother-infant interaction (N = 255; 2-6 months), predicted poorer infant inhibitory control at 19-28 months. However, infants who exhibited high visual orienting behavior (VOB) under high unpredictability showed later inhibitory control comparable to infants exposed to low unpredictability, suggesting an adaptive behavioral buffering strategy. In a subset of infants (n = 87), we tested whether infant age, sex, delivery mode, feeding, maternal education, and maternal unpredictability explained variation in gut microbial community diversity. Only feeding status and VOB were significantly associated with both taxonomic and functional microbial profiles. VOB was associated with taxonomic and functional variation along a Bifidobacterium breve and Bifidobacterium longum axis and enrichment of microbial tryptophan and glutamate synthesis genes. Although feeding groups differed in alpha diversity, VOB was not associated with feeding status, suggesting that feeding is not the primary driver of the observed VOB-microbiome signatures. Interaction models of neuroactive gene functions revealed that microbial signatures vary across combinations of VOB and maternal unpredictability, suggesting that the microbial support for deploying visual attentional strategies differs under distinct levels of environmental unpredictability. Together, these findings support a framework in which infant behavioral strategy is associated with variation in gut microbial composition and metabolic gene potential.