Early-life exposure to toxic and nutrient elements in relation to the infant microbiome as a possible mediator or modifier of autism-related social behaviors

Abstract

Background/Aim: In our previous analysis in the New Hampshire Birth Cohort Study, we identified associations between nutrient-toxic element mixtures and the early-life microbiome. The role of nutrient toxic mixtures and microbiome changes are being examined for their associations with autism-related social behaviors at age three years. However, there is limited information on the extent to which the microbiome mediates or modifies the association between a broader range environmental elements and childhood behaviors.Methods: In a subset of infants from a prospective birth cohort, six-week-old toenail clippings were analyzed for eleven elements (manganese, iron, nickel, copper, zinc, arsenic, selenium, cadmium, tin, mercury, and lead) using inductively coupled plasma mass spectrometry. Stool samples were collected from diapers at six weeks and one year of age, metagenomic sequencing was performed, and taxa/gene functions were inferred following established pipelines. At three years, parents completed the Social Responsiveness Scale, 2nd Edition (SRS-2), which assesses the frequency of autism-related social behaviors (higher scores indicate worse behavior). Covariates were determined a priori, and a complete case analysis was conducted.Results: Both nutrient and toxic elements were associated with microbial taxa in six-week-old and one-year-old stools, but none of these taxa was also associated with social behaviors. Arsenic and tin were associated with decreased relative abundance of vitamin B6 biosynthesis genes (PWY0-845) in one-year-old stools, increased abundance of which was found to be negatively associated with SRS-2 total T-scores. In contrast, lead was associated with increased relative abundance of PWY0-845 in six-week-old stools, which was also found to be negatively associated with SRS-2 total T-scores. Formal mediation/modification analyses based on these preliminary findings is underway.Conclusions: Investigation of the potential mediating or modifying role of microbiome may help to elucidate the mechanisms by which environmental exposures influence autism-related social behaviors.