Maternal Exposure to Endocrine-Disrupting Chemicals: Analysis of Their Impact on Infant Gut Microbiota Composition

Abstract

Endocrine disruptors (EDCs) are chemicals that interfere with the endocrine system. EDC exposure may contribute to the development of obesity, type 2 diabetes, and cardiovascular diseases by impacting the composition of an infant's gut microbiota during the first 1000 days of life. To explore the relationship between maternal urinary levels of Bisphenol-A and phthalates (UHPLC-MS/MS), and the composition of the infant gut microbiota (16S rDNA) at age 12 months (T₃) and, retrospectively, at birth (T₀), 1 month (T₁), and 6 months (T₂), stool samples from 20 infants breastfed at least once a day were analyzed. Metataxonomic bacteria relative abundances were correlated with EDC values. Based on median Bisphenol-A levels, infants were assigned to the over-exposed group (O, n = 8) and the low-exposed group (B, n = 12). The B-group exhibited higher gut colonization of the Ruminococcus torques group genus and the O-group showed higher abundances of Erysipelatoclostridium and Bifidobacterium breve. Additionally, infants were stratified as high-risk (HR, n = 12) or low-risk (LR, n = 8) exposure to phthalates, based on the presence of at least three phthalates with concentrations exceeding the cohort median values; no differences were observed in gut microbiota composition. A retrospective analysis of gut microbiota (T₀-T₂) revealed a disparity in β-diversity between the O-group and the B-group. Considering T₀-T₃, the Linear Discriminant Effect Size indicated differences in certain microbes between the O-group vs. the B-group and the HR-group vs. the LR-group. Our findings support the potential role of microbial communities as biomarkers for high EDC exposure levels. Nevertheless, further investigations are required to deeply investigate this issue.

Keywords: bisphenol a; breastfeeding; endocrine disrupting chemicals; first 1000 days; gut microbiota; phthalates.

Figure 1

Based on Spearman’s rank correlation, significant (p < 0.05) correlation scores between the relative abundance of gut microbes found in stool samples of infants breastfed at least one a day up to 12 months of age and the EDC concentrations found in maternal urinary samples. Before the taxon name, the taxonomy level of the relative ASV (g, genus or s, species) is shown.

Figure 2

Gut microbiota differences between infants of mothers highly exposed to BPA (O group; BPA maternal levels > 0.96 µg/g creatinine) and infants of mothers less exposed to BPA (B group; BPA maternal levels ≤ 0.96 µg/g creatinine).

Figure 3

Based on the LefSe method, metataxonomic differences in fecal microbiota of infants: (panel (A)) breastfed by mothers showing urinary BPA concentrations over (O) or below (B) the BPA median value, (panel (B)) at high−risk (HR) and low−risk (LR) exposure to phthalates.

Figure 4

Volcano plot illustrating the upregulated (in red) and downregulated (in blue) KEGG pathway relative frequencies in infants exposed to elevated levels of BPA. Boxplots display normalized values of KEGG pathway relative frequencies, with B indicating B−group infants and O representing O−group infants. Significance was achieved for pathways exhibiting a fold change (FC) > 2 (log2) and a p-value < 0.05 (expressed as –log₁₀).

Figure 5

Volcano plot illustrating upregulated (in red) KEGG pathway relative frequencies in infants exposed to a high risk (HR) of endocrine-disrupting chemicals (EDCs). Boxplots, with red denoting HR–infants and blue representing LR–infants, display normalized values of KEGG pathway relative frequencies. Significance was attained for pathways exhibiting both a fold change (FC) > 2 (expressed as log2) and a p-value < 0.05 (expressed as –log10).