Abstract
Arsenic is related to neurodevelopmental outcomes and is associated with the composition of the gut microbiome. Data on the modifying role of the microbiome are limited. We probed suggestive relationships between arsenic and social behaviors to quantify the modifying role of the infant gut microbiome. We followed children for whom arsenic concentrations were quantified in 6-week-old toenail clippings. Scores on the Social Responsiveness Scale (SRS-2), which measures autism-related social behaviors, were provided by caregivers when the child was approximately 3 years of age. Metagenomic sequencing was performed on infant stools collected at 6 weeks and 1 year of age. To evaluate modification by the top ten most abundant species and functional pathways, we modeled SRS-2 total T-scores as a function of arsenic concentrations, microbiome features dichotomized at their median, and an interaction between exposure and the microbiome, adjusting for other trace elements and sociodemographic characteristics. As compared to the standardized population (SRS-2 T-scores = 50), participants in our study had lower SRS-2 scores (n = 78, mean = 44, SD = 5).The relative abundances of several functional pathways identified in 6-week stool samples modified the arsenic–SRS-2 association, including the pathways of valine and isoleucine biosynthesis; we observed no association among those with high relative abundance of each pathway [β = − 0.67 (95% CI − 1.46, 0.12)], and an adverse association [β = 1.67 (95% CI 0.3, 3.04), pinteraction = 0.05] among infants with low relative abundance. Our findings indicate the infant gut microbiome may alter neurodevelopmental susceptibility to environmental exposures.
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Data Availability
Raw fecal sample sequences are available through the National Center for Biotechnology Information Sequence Read Archive (https://ncbi.nlm.nih.gov/sra) under accession number PRJNA296814. Epidemiologic data are not publicly available due to their sensitive and identifiable nature. Detailed code is available upon request from Hannah E. Laue (Hannah.E.Laue@dartmouth.edu). Requests to work with the New Hampshire Birth Cohort Study should be directed to Margaret R. Karagas (Margaret.R.Karagas@Dartmouth.edu).
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Funding
This study was supported by the National Institute of Environmental Health under Grants P01ES022832, P20ES018175, and P42ES007373; the National Institute of General Medical Sciences under Grant P20GM104416; the National Institutes of Health Office of the Director under Grants UG3OD023275 and UH3OD023275 and the U.S. Environmental Protection Agency under Grant RD-83544201.
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HEL, JCM, and MRK conceptualized and developed the methodology for the study. HEL performed the formal analysis and visualization. BPJ, TJP, ERB, SAK, JCM, and MRK provided resources. YM performed data curation. HEL wrote the original draft of the manuscript. All authors reviewed and edited the final version of the manuscript. MRK acquired funding.
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Laue, H.E., Moroishi, Y., Jackson, B.P. et al. Bacterial Modification of the Association Between Arsenic and Autism-Related Social Behavior Scores. Expo Health 15, 347–354 (2023). https://doi.org/10.1007/s12403-022-00494-0
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DOI: https://doi.org/10.1007/s12403-022-00494-0