Akkermansia muciniphila modifies the association between metal exposure during pregnancy and depressive symptoms in late childhood.

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.