Association between\nExposure to Metals during Pregnancy,\nChildhood Gut Microbiome, and Risk of Intestinal Inflammation in Late\nChildhood

Alterations\nto the gut microbiome and exposure to metals\nduring\npregnancy have been suggested to impact inflammatory bowel disease.\nNonetheless, how prenatal exposure to metals eventually results in\nlong-term effects on the gut microbiome, leading to subclinical intestinal\ninflammation, particularly during late childhood, has not been studied.\nIt is also unknown whether such an interactive effect drives a specific\nsubgroup of children toward elevated susceptibility to intestinal\ninflammation. We used an amalgamation of machine-learning techniques\nwith a regression-based framework to explore if children with distinct\nsets of gut microbes and certain patterns of exposure to metals during\npregnancy (metal–microbial clique signature) had a higher likelihood\nof intestinal inflammation, measured based on fecal calprotectin (FC)\nin late childhood. We obtained samples from a well-characterized longitudinal\nbirth cohort from Mexico City (<i>n</i> = 108), Mexico.\nIn the second and third trimesters of pregnancy, 11 metals were measured\nin whole blood. Gut microbial abundances and FC were measured in stool\nsamples from children 9–11 years of age. Elevated FC was defined\nas having FC above 100 μg/g of stool. We identified subgroups\nof children in whom microbial and metal–microbial clique signatures\nwere associated with elevated FC (false discovery rate (FDR) <\n0.05). In particular, we found two metal–microbial clique signatures\nsignificantly associated with elevated FC: (1) low cesium (Cs) and\ncopper (Cu) in the third trimester and low relative abundance of <i>Eubacterium ventriosum</i> (OR [95%CI]: 10.27 [3.57,29.52],\nFDR < 0.001) and (2) low Cu in the third trimester and high relative\nabundances of <i>Roseburia inulinivorans</i> and <i>Ruminococcus torques</i> (OR [95%CI]: 7.21 [1.81,28.77], FDR\n< 0.05). This exploratory study demonstrates that children with\nspecific gut microbes and specific exposure patterns to metals during\npregnancy may have higher fecal calprotectin levels in late childhood,\ndenoting an elevated risk of intestinal inflammation.