Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population

Abstract

Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome composition at 6 weeks of life (p = 0.05, adjusted for infant feeding type and urine specific gravity). Eight genera, six within the phylum Firmicutes, were enriched with higher arsenic exposure. Fifteen genera were negatively associated with urinary arsenic concentration, including Bacteroides and Bifidobacterium. Upon stratification by both sex and feeding method, we found detectable associations among formula-fed males (p = 0.008), but not other groups (p > 0.05 for formula-fed females and for breastfed males and females). Our findings from a US population indicate that even moderate arsenic exposure may have meaningful, sex-specific effects on the gut microbiome during a critical window of infant development.

Figure 1

Principal coordinate plot of generalized UniFrac distance matrix comparing microbiome community profiles according to urinary arsenic concentration. (a) All N = 204 infants in the study; (b) N = 33 formula-fed males. Corresponding plots for other groups are presented in the supplementary information (Fig. S1). Statistical testing was performed using a continuous measure of arsenic exposure, the natural log of urinary arsenic concentration; however, for visualization purposes, here subjects were divided at the median urinary arsenic concentration of 0.36 μg/L.

Figure 2

Cladogram showing bacterial OTUs with differential relative abundances based on arsenic levels. Color-shaded areas of the cladogram delineate the most abundant phyla in the infant gut microbiota, with the size of corresponding nodes proportional to the abundance level of the clades. Several OTUs were significantly associated with arsenic levels; bars in the outer rings identified individual OTUs that were positively (blue bars) and negatively (red bars) correlated with urine arsenic concentrations. Rings correspond to all infants in the study (N = 204), male formula-fed infants only (N = 33), female formula-fed infants only (N = 23), male exclusively breastfed infants only (N = 85) and female exclusively breastfed infants only (N = 58).

Figure 3

Mean UniFrac distances between pairs of samples that are in extreme quartiles of urinary arsenic for all babies who were formula-fed, for formula-fed males only and for formula-fed females only. Bars represent bootstrapped 95% confidence intervals around the means.