Perinatal & Pediatric
Akkermansia muciniphila modifies the association between prenatal metal exposure and childhood depressive symptoms Kiran P. Nagdeo* Kiran P. Nagdeo Vishal Midya Jamil Lane Libni A. Torres-Olascoaga Gabriela Gil Martínez Megan K. Horton Chris Gennings Martha Maria Téllez-Rojo Robert O. Wright Manish Arora Shoshannah Eggers
Background: Emerging research suggests that prenatal metal exposure and gut microbiome (GM) disruptions are associated with depressive disorders. Akkermansia muciniphila, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in influencing the association between prenatal metal exposures and depressive symptoms in later childhood is not known. We investigated whether the presence of A. mucinipnila in the GM of 9-11-year-olds modifies the associations between specific groups of prenatal metal exposures (metal-clique) and concurrent depressive symptoms.
Methods: We leveraged 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 GM assessment by metagenomic sequencing. A. muciniphila presence was detected using GM data. Children’s Depression Inventory (CDI) was administered to 9-11-year-olds. We used a combination of interpretable machine learning and regression framework to identify specific groups of prenatal metals that are predictive and associative with depressive symptoms.
Results: We identified a three-component metal-clique consisting of high Zn and low Cr in the second trimester and low Co in the third trimester, characterizing a sub-group of 40.9% children. This metal-clique was significantly associated with increased log-transformed, t-scored CDI score (log-tCDI)(b[95%CI]=0.08[0.02,0.13]). The presence of A. muciniphila was associated with significantly decreased log-tCDI(b[95%CI]= -0.13[-0.21,-0.04]). Among children with no A. muciniphila, this metal-clique was significantly associated with increased log-tCDI (b[95%CI]=0.11[0.05,0.18]); whereas, for children with A. muciniphila, this same metal-clique, was associated with decreased depression score (b[95%CI]=-0.05[-0.16,0.06]).
Conclusion: We found suggestive evidence that A. muciniphila may modify the association between prenatal exposure to a particular group of metals (or metal-clique) and depressive symptoms in late childhood.
