Longitudinal changes during pregnancy in gut microbiota and methylmercury biomarkers, and reversal of microbe-exposure correlations

Abstract

Objective: Gut microorganisms contribute to the metabolism of environmental toxicants, including methylmercury (MeHg). Our main objective was to investigate whether associations between biomarkers for prenatal MeHg exposure and maternal gut microbiota differed between early and late gestation.

Methods: Maternal blood and stool samples were collected during early (8.3-17 weeks, n=28) and late (27-36 weeks, n=24) gestation. Total mercury and MeHg concentrations were quantified in biomarkers, and inorganic mercury was estimated by subtraction. The diversity and structure of the gut microbiota were investigated using 16S rRNA gene profiling (n = 52). Biomarkers were dichotomized, and diversity patterns were compared between high/low mercury concentrations. Spearman's correlation was used to assess bivariate associations between MeHg biomarkers (stool, blood, and meconium), and 23 gut microbial taxa (genus or family level, >1% average relative abundance).

Results: Within-person and between-person diversity patterns in gut microbiota differed between early/late gestation. The overall composition of the microbiome differed between high/low MeHg concentrations (in blood and stool) during early gestation, but not late gestation. Ten (of 23) taxa were significantly correlated with MeHg biomarkers (increasing or decreasing); however, associations differed, depending on whether the sample was collected during early or late gestation. A total of 43% of associations (69/161) reversed the direction of correlation between early/late gestation.

Conclusions: The time point at which a maternal fecal sample is collected may yield different associations between gut microorganisms and MeHg biomarkers, which may be due in part to remodeling of maternal microbiota during pregnancy. Our results suggest the effectiveness of dietary interventions to reduce prenatal MeHg exposure may differ between early and late gestation.

Keywords: Gut microbiota; Meconium; Methylmercury; Prenatal.

Figure 1.

Bivariate associations between log₁₀ meconium MeHg and a) log₁₀ maternal blood MeHg and b) log₁₀ maternal stool MeHg. Maternal stool and blood samples were collected during early (black circles, solid line) and late (open circles, broken line) gestation (n=17 paired samples at each time point). P-values are for Pearson's correlation.

Figure 2.

Within class Principal Coordinate Analysis (PCoA) showing community structure (β-diversity) assessed by Jensen-Shannon diversity distances controlling for subject effect. Composition of bacterial communities during late gestation (n=24) were significantly different compared to early gestation (n=28) when accounting for the repeated measures of same subjects (T_w² test, p=0.03).

Figure 3.

Spearman's correlation between gut microbiota phyla, and fish meals (meals/weekly), stool methylmercury (MeHg) (ng/g), stool inorganic mercury (IHg) (ng/g), stool IHg (% of THg), meconium (Mec) MeHg, blood MeHg (μg/L), blood IHg (μg/L), and plasma vitamin D (25-hydroxy-vitamin D) (ng/mL), during a) early gestation and b) late gestation. During early gestation n=28, except vitamin D (n=22), and meconium MeHg (n=17). During late gestation n=24, except vitamin D (n=21), and meconium (n=17). Note that fish meals and meconium did not differ between early and late gestation, whereas biomarkers for stool and blood MeHg and IHg, and plasma vitamin D were analyzed at each time point. "x" p<0.05.

Figure 4.

Spearman's correlation between gut microbiota taxa (family or genus level, >1% average abundance), and fish meals (meals/weekly), stool methylmercury (MeHg) (ng/g), stool inorganic mercury (IHg) (ng/g), stool IHg (% of THg), meconium (Mec) MeHg, blood MeHg (μg/L), blood IHg (μg/L), and plasma vitamin D (25-hydroxy-vitamin D) (ng/mL), during a) early gestation and b) late gestation. During early gestation n=28, except vitamin D (n=22), and meconium MeHg (n=17). During late gestation n=24, except vitamin D (n=21), and meconium (n=17). Note that fish meals and meconium did not differ between early and late gestation, whereas biomarkers for stool and blood MeHg and IHg, and plasma vitamin D were analyzed at each time point. "x" p<0.05, "xx" p<0.01.