Abstract
Emerging research suggests that exposures to metals during pregnancy and gut microbiome (GM) disruptions are associated with depressive disorders in childhood. Akkermansia muciniphila, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in the influence of prenatal metal exposures on depressive symptoms during childhood is unknown. Leveraging a well-characterized pediatric longitudinal birth cohort and its microbiome substudy (n=112) and using a state-of-the-art machine-learning model, we investigated whether the presence of A.muciniphila in GM of 9-11-year-olds modifies the associations between exposure to a specific group of metals (or metal-clique) during pregnancy and concurrent childhood depressive symptoms. Among children with no A.muciniphila, a metal-clique of Zinc-Chromium-Cobalt was strongly associated with increased depression score (P<0.0001), whereas, for children with A.muciniphila, this same metal-clique was weakly associated with decreased depression score(P<0.4). Our analysis provides the first exploratory evidence hypothesizing A. muciniphila as a probiotic intervention attenuating the effect of prenatal metal-exposures-associated depressive disorders in late childhood.