Prenatal Alcohol Exposure Selectively Induces Gut Microbiota Alterations in male adolescent C57Bl/6 Mice

However, the GM’s role in FASD is still poor explored. This study aimed to examine how early PAE affects the GM of adolescent offspring to identify potential targets for early diagnosis or treatment.

Methods

Female C57Bl/6 mice were exposed to 10% ethanol solution during the first 10 days of pregnancy, and then to water for the rest of gestation (PAE group). Control mice received only water throughout their entire pregnancy (Control group). Fecal and blood samples were collected to analyze GM composition and short-chain fatty acids (SCFAs), using 16S rRNA gene sequencing and gas chromatography-mass spectrometry.

Results: PAE mice showed a significant reduction in alpha diversity and notable changes in beta diversity of their GM compared to controls. Gender analysis revealed that PAE males had distinct microbial genera compared to controls, with significant increases in Bacteroides, Bilophila and Clostridioides. Moreover, fecal analysis in males revealed higher levels of isobutyric, isovaleric, and 2-methylbutyric acids—metabolites known for their anti-inflammatory properties.

Conclusions: These results suggest that PAE causes sex-specific alterations in the microbiota-gut- brain axis, highlighting the gut microbiota as a promising target for preventive or supportive therapies aimed at reducing the cognitive and behavioral impairments linked to FASD.