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