Akkermansia muciniphila may mediate the association between prenatal metal mixture exposure and childhood depressive symptoms

Abstract

Abstract Background: Prenatal metal exposure may be associated with childhood depressive symptoms. Emerging research suggests links between gut microbiome (GM) disruptions and depressive disorders. Akkermansia muciniphila, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in mediating the association between prenatal metal exposures and depressive symptoms in later childhood is not known. We aim to estimate the associations between prenatal mixed metal exposures, A. mucinipnila presence in the gut microbiome at 9-11 years old, and concurrent depressive symptoms. Methods: We leverage existing data from a subset of 112 participants in the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort. Metal concentrations (Pb, As, Cd, Cr, Zn, Se, Sb, Cu, Cs, Co, Mn) were measured in 2nd and 3rd trimester maternal whole blood. Stool samples were collected at 9–11 years of age and underwent metagenomic sequencing to assess the GM. The presence of A. muciniphila was detected using GM data. Children’s Depression Inventory (CDI) was administered at 9-11 years. We used weighted quantile sum (WQS) regression to separately estimate associations between prenatal metal mixture exposure at 2nd and 3rd trimesters and CDI. We used a nonparametric bootstrap approach to estimate the proportion of these associations mediated by A. muciniphila. Results: A. muciniphila was detected in 24% of participants. The presence of A. muciniphila was associated with a significantly decreased log-transformed, t-score normalized CDI score (log tCDI) (ß=-0.13, 95%CI=[-0.21,-0.04]), suggesting a protective effect. Second and 3rd-trimester metal mixtures were associated with increased log tCDI (ß=0.06 per increase in quartile, 95%CI=[0.01,0.10] and ß=0.03 per increase in quartile, 95%CI=[-0.02,0.09], respectively). A quartile increase in these metal mixtures trended towards decreased odds of A. muciniphila (OR=0.54, 95%CI=[0.23,1.24] and OR=0.58, 95%CI=[0.23,1.49] at 2nd and 3rd trimesters respectively). The presence of A. muciniphila may mediate the association between the 2nd-trimester metal mixture and log tCDI by 34%. Conclusion: We found suggestive evidence that A. muciniphila may attenuate the association between prenatal metal exposures and childhood depressive symptoms. A. muciniphila supplementation may be a promising intervention strategy to mitigate metal-associated depressive symptoms. Additional studies are needed to confirm these findings.