Early-life arsenic exposure modulates the developing microbiome in a rural cohort

Studies reported associations between arsenic and the infant gut microbiome measured contemporaneously. We tested the hypothesis that early-life arsenic associates with longitudinal microbiome differences and examined sex-specific effects.

Participants provided urine and fecal samples at six weeks (6W; n = 219) or twelve months (12M; n = 219), a subset of whom provided samples at both (n = 167). Total arsenic (tAs), inorganic arsenic, monomethylarsinic acid, and dimethylarsinic acid (DMA) were quantified in 6W and 12M urine with high-performance liquid chromatography with inductively-coupled plasma mass spectrometry. We estimated gut microbiome composition at 6W and 12M with metagenomic sequencing. Using generalized linear and mixed-effect models, we evaluated cross-sectional and longitudinal associations of arsenic concentrations with bacterial diversity and species/gene pathway relative abundance.

DMA and tAs at 6W were associated with bacterial species at 6W but similar associations were not observed at 12M. At 6W, associations between arsenic and metabolic pathways tended to be sex-specific. In longitudinal analyses, tAs associated with higher Shannon diversity [β = 0.07 per doubling (95 %CI: 0.05, 0.09)], with a diminishing trend in this association with sampling age [β = -0.04 per doubling (95 %CI: 0.07, -0.004)]. We observed a similar longitudinal pattern between at least one arsenic measure and ten bacterial species, with stronger associations among males than females.

We observed longitudinal and cross-sectional associations of arsenic and the gut microbiome in the first year of life. Early-life arsenic concentrations were more strongly associated with disruptions in the infant gut microbiome than later infancy, highlighting the importance of early-life exposures in microbiome dysbiosis.