Metal mixtures and oral health among children and adolescents in the National Health and Nutrition Examination Survey (NHANES), 2017-2020.

INTRODUCTION: Dental caries is the most common non-communicable human disease, yet little is known about the role of environmental metals, despite teeth consisting of a hard matrix of trace elements. We conducted a cross-sectional study of associations between environmental metals and objective assessment of dental caries and subjective assessments of oral health among a representative sample of U.S. children and adolescents. METHODS: Data were from the 2017-March 2020 pre-pandemic data file of the National Health and Nutrition Examination Survey (NHANES). To account for metal mixtures, we used weighted quantile sum (WQS) regression to estimate the joint impact of multiple trace elements assessed in blood and urine with oral disease outcomes. RESULTS: The blood metal mixture index was associated with a 32% (95% CI: 1.11, 1.56) increased risk of decayed surfaces while the urine metal mixture index was associated with a 106%, RR (95% CI = 2.06 (1.58, 2.70) increased caries risk. For both blood and urine, Mercury (Hg) had the largest contribution to the mixture index followed by Lead (Pb). The WQS blood metal mixture index was also significantly associated with poorer self-rated oral health, although the magnitude of the association was not as strong as for the objective oral disease measures, RR (95% CI) = 1.04 (1.02, 1.07). DISCUSSION: Increased exposure to a metal mixture was significantly related to poorer objective and subjective oral health outcomes among U.S. children and adolescents. These are among the first findings showing that metal mixtures are a significant contributor to poor oral health.

Prenatal Pb exposure is associated with reduced abundance of beneficial gut microbial cliques in late childhood: an investigation using Microbial Co-occurrence Analysis (MiCA).

Background: Many analytical methods used in gut microbiome research focus on either single bacterial taxa or the whole microbiome, ignoring multi-bacteria relationships (microbial cliques). We present a novel analytical approach to identify multiple bacterial taxa within the gut microbiome of children at 9-11 years associated with prenatal Pb exposure. Methods: Data came from a subset of participants (n=123) in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort. Pb concentrations were measured in maternal whole blood from the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the gut microbiome. Using a novel analytical approach, Microbial Co-occurrence Analysis (MiCA), we paired a machine-learning algorithm with randomization-based inference to first identify microbial cliques that were predictive of prenatal Pb exposure and then estimate the association between prenatal Pb exposure and microbial clique abundance. Results: With second-trimester Pb exposure, we identified a 2-taxa microbial clique that included Bifidobacterium adolescentis and Ruminococcus callidus, and a 3-taxa clique that added Prevotella clara. Increasing second-trimester Pb exposure was associated with significantly increased odds of having the 2-taxa microbial clique below the 50th percentile relative abundance (OR=1.03,95%CI[1.01-1.05]). In an analysis of Pb concentration at or above vs. below the United States and Mexico guidelines for child Pb exposure, odds of the 2-taxa clique in low abundance were 3.36(95%CI[1.32-8.51]) and 6.11(95%CI[1.87-19.93]), respectively. Trends were similar with the 3-taxa clique but not statistically significant. Discussion: Using a novel combination of machine-learning and causal-inference, MiCA identified a significant association between second-trimester Pb exposure and reduced abundance of a probiotic microbial clique within the gut microbiome in late childhood. Pb exposure levels at the guidelines for child Pb poisoning in the United States, and Mexico are not sufficient to protect against the potential loss of probiotic benefits.