Impact of lactational per- and polyfluoroalkyl substances exposure on infant gut microbiota and potential mediating effects on infant neurodevelopment
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Xin Zhang1, Huijun Chen2, Peng Liu1
1Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan 430071, PR China.
Insights
Exposure to per- and polyfluorinated substances (PFAS) in breast milk is linked to lower infant neurodevelopmental scores. Gut bacteria disruption by PFAS may explain these delays, suggesting a potential therapeutic target for infant health.
Area of Science:
- Environmental Health
- Neurodevelopmental Science
- Microbiome Research
Background:
- Per- and polyfluorinated substances (PFAS) exposure is linked to adverse maternal and infant health outcomes.
- The impact of PFAS on infant neurodevelopmental trajectories is not well understood.
- Human milk and infant gut microbiome are critical for early development.
Purpose of the Study:
- To investigate the association between lactational PFAS exposure and infant neurodevelopment.
- To explore the role of the infant gut microbiome as a mediator in PFAS-induced neurodevelopmental effects.
- To identify specific PFAS compounds and microbial species involved in these associations.
Main Methods:
- Longitudinal study of 114 mother-infant pairs with sample collection at 0.5, 1, and 3 months postpartum.
- Analysis of human milk and infant fecal samples for PFAS concentrations and gut microbiome composition.
- Infant neurodevelopmental assessment at 6 months using Ages & Stages Questionnaires Third Edition and Social-Emotional scales.
Main Results:
- Higher concentrations of specific PFAS (PFOS, PFOA) in human milk correlated with lower infant scores across multiple neurodevelopmental domains (communication, motor skills, problem-solving, social-personal).
- PFAS exposure, particularly long-chain variants and PFOS, altered the infant gut microbiome, increasing harmful bacteria (e.g., Klebsiella variicola, Enterococcus faecium, Clostridium perfringens) and decreasing beneficial ones (e.g., Bifidobacterium breve, Streptococcus).
- Mediation analysis indicated that gut bacteria like Clostridium perfringens and Streptococcus partially explained the link between PFAS exposure and fine motor/gross motor deficits, respectively.
Conclusions:
- Lactational exposure to PFAS is associated with impaired infant neurodevelopmental outcomes.
- The infant gut microbiome acts as a mechanistic link between PFAS exposure and neurodevelopmental delays.
- Targeting the gut microbiota may offer a novel therapeutic strategy to mitigate the adverse neurodevelopmental effects of PFAS exposure in infants.
Abstract:
Exposure to per- and polyfluorinated substances (PFAS) is associated with adverse maternal and infant health effects, particularly undesirable birth outcomes. Whether PFAS affects neurodevelopmental trajectories remains unknown. This longitudinal study enrolled 114 mother-infant pairs, analyzing longitudinally collected human milk and infant fecal samples at 0.5, 1, and 3 months postpartum. Infant neurodevelopment was assessed using the Ages & Stages Questionnaires Third Edition and the Social-Emotional at 6 months of age. Increasing concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), 2-(N-Methylperfluorooctanesulfonamido) acetic acid and PFAS mixture overall in human milk were associated with significantly lower scores in communication, gross motor, fine motor, problem solving, and personal-social domains. Moreover, long-chain perfluoroalkyl carboxylic acids and PFOS disrupted the establishment of the early infant gut microbiome, resulting in increased relative abundances of Klebsiella variicola, Enterococcus faecium, Clostridium perfringens, and Veillonella atypica. During this developmental period, perfluorononanoic acid (PFNA), PFOS, and its substitute perfluoro2-((6-chlorohexyl) oxy) ethane sulfonic acid also decreased the abundance of Bifidobacterium breve and Streptococcus. Mediation analysis further revealed that Clostridium perfringens mediated 13 % of ΣPFAS exposure's effect on fine motor and Streptococcus mediated 11 % of PFOS exposure's effect on gross motor deficits. These findings establish gut microbiota as a mechanistic link between lactational PFAS exposure and neurodevelopmental delays, identifying the microbiota as a potential therapeutic target.
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