Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition

Abstract

Background: Human milk is rich in essential nutrients and immune-activating compounds but is also a source of toxicants including per- and polyfluoroalkyl substances (PFAS). Evidence suggests that immune-related effects of PFAS may, in part, be due to alterations of the microbiome. We aimed to identify the association between milk PFAS exposure and the infant gut microbiome. Methods: PFAS [perfluorooctane sulfonic acid (PFOS) and perfluorooctanoate (PFOA)] were quantified in milk from ~6 weeks postpartum using high-performance liquid chromatography with tandem mass spectrometry. A molar sum (ΣPFAS) was calculated. Caregivers collected infant stool samples at 6 weeks (n = 116) and/or 1 year postpartum (n = 119). Stool DNA underwent metagenomic sequencing. We estimated the association of PFAS with diversity and relative abundances of species with linear regression. Single- and multi-PFAS models adjusted for potential confounders in complete case analyses and with imputed missing covariate data for 6-week and 1-year microbiomes separately. We assessed sensitive populations with stratification. Results: PFOS and PFOA were detected in 94% and 83% of milk samples, respectively. PFOS was associated with increased diversity at 6 weeks among infants fed exclusively human milk [β = 0.24 per PFOS doubling, (95% CI = 0.03, 0.45), P = 0.03] and born to primiparous mothers [β = 0.37 (0.06, 0.67), P = 0.02]. Estimates were strongest in multi-PFAS models and among complete cases. ΣPFAS was associated with Bacteroides vulgatus relative abundance at 1 year [(β = –2.34% per doubling (–3.63, –1.05), FDR q = 0.099]. Conclusions: PFAS may increase infant gut microbiome diversity and alter the relative abundance of biologically relevant bacteria. Additional analyses may identify related health outcomes.

An in vitro model system for testing chemical effects on microbiome-immune interactions – examples with BPX and PFAS mixtures

“…In addition to BPX, other environmental chemicals have been the focus of microbiome studies, including PFAS. Evidence for their potential to disrupt the microbiota is already available from epidemiological studies ( 39 ). Furthermore, exposure to PFOA significantly altered the gut microbiota of mice, with an increase in Bacteroidetes and a decrease in fecal short-chain fatty acid (SCFA) concentrations, suggesting consequences of PFAS exposure at both the taxonomic and functional levels ( 40 , 41 ).…”

Impact of Exposure to Per- and Polyfluoroalkyl Substances on Fecal Microbiota Composition in Mother-Infant Dyads

“…Importantly, we do not yet understand the potential of PFAS to alter the human gut microbiome at the individual species level. Recently, in a US pregnancy cohort, impact of milk PFAS concentrations on gut microbiome were accessed at bacterial species level in the infants (Laue et al, 2023). However, not much is known about the impact of PFAS on the paired maternal-child samples.…”