Embryonic exposure to 6:2 fluorotelomer alcohol mediates autism spectrum disorder-like behavior by dysfunctional microbe-gut-brain axis in mice

J Hazard Mater. 2025 Feb 15:484:136739. doi: 10.1016/j.jhazmat.2024.136739. Epub 2024 Dec 1.

Abstract

6:2 fluorotelomer alcohol (6:2 FTOH) is considered an emerging contaminant as a substitute for perfluoroalkyl and polyfluoroalkyl substances. Autism spectrum disorder (ASD) is a highly heterogeneous childhood neurodevelopmental disorder, the prevalence of which has been significantly increasing globally, possibly due to rising exposure to environmental pollutants. Additionally, the microbe-gut-brain axis plays a crucial role in the development of ASD. The purpose of study was to investigate the impact of embryonic 6:2 FTOH exposure on neurological development in mice and explore the potential involvement of the microbe-gut-brain. Pregnant mice were orally administered 6:2 FTOH from gestation day 8.5 until delivery, and follow-up testing was performed on day 22 post-delivery. The findings revealed that embryonic exposure to 6:2 FTOH led to ASD-like symptoms, cortical neuron apoptosis, glial cell activation, and abnormal synapse formation in mice. Furthermore, impairment of colonic barrier function, inflammatory response, and dysbiosis in gut microbiota were observed. Interestingly, supplementation with Lactobacillus rhamnosus GG during embryonic development mitigated these adverse outcomes. This study enhances our understanding of how environmental pollutants can impact neurological development in children and provides valuable insights for clinical prevention, diagnosis, and treatment strategies for non-genetic ASD.

Keywords: 6:2 fluorotelomer alcohol; Autism spectrum disorder; Gut microbiota dysbiosis; Lactobacillus rhamnosus GG; Microbe-gut-brain axis.

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / chemically induced
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain-Gut Axis* / drug effects
  • Dysbiosis / chemically induced
  • Female
  • Fluorocarbons* / toxicity
  • Gastrointestinal Microbiome* / drug effects
  • Lacticaseibacillus rhamnosus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Prenatal Exposure Delayed Effects

Substances

  • Fluorocarbons