“Fetal Alcohol Spectrum Disorder (FASD) is a range of neurodevelopmental abnormalities caused by Perinatal Alcohol Exposure (PAE), leading to profound behavioral and molecular disturbances in the offspring. Unraveling the central and peripheral mechanisms involved, including the microbiota-gut-brain axis, is crucial to improving our understanding of the disease and developing new treatment strategies from a sex perspective.
In this study, we investigated the impact of PAE on emotional behavior, brain biomarkers, and gut microbiota composition and diversity in a preclinical C57BL/6 J mouse model, as well as the extent of their vulnerability to alcohol consumption. Furthermore, we have also explored the potential modulatory effects of cannabidiol (CBD) administered chronically (30 mg/kg/day, i.p.) from weaning on PAE-induced sex-dependent emotional and brain molecular impairments, gut microbiota dysbiosis, and increased alcohol reinforcing and motivational actions.
FASD model mice showed increased anxiety- and depressive-like behavior accompanied by sex-dependent changes in synaptic density, dopamine D2/D3 receptors availability, cannabinoid receptors 1 and 2 (Cnr1/Cnr2), tyrosine hydroxylase (Th), and serotonin transporter (Slc6a4) gene expression, and gut microbiota dysbiosis.
Interestingly, CBD sex-dependently improved and/or normalized PAE-induced behavioral and molecular disturbances. In addition, females but not males exposed to the animal model of FASD showed a higher motivation to drink alcohol, which CBD abolished.
Our findings provide new insights into the brain and gut microbiota sex-dependent mechanisms involved in FASD pathophysiology and further highlight the therapeutic potential of CBD to improve the management of FASD-induced emotional disturbances and alcohol addiction from a sex-oriented approach.”
https://pubmed.ncbi.nlm.nih.gov/41273930
“FASD model mice displayed emotional disturbances (anxiety- and depressive-like behaviors), which CBD alleviated.”
“Together, our findings reveal that PAE profoundly alters gut microbiota and that CBD can modulate this dysbiosis, promoting beneficial taxa and modifying community structure in a sex-dependent manner.
CBD administration also mitigated anxiety- and depression-like behaviors and modulated gene expression of endocannabinoid and monoaminergic markers.
This study opens the door to the development of personalized interventions aimed at restoring the microbiota and modulating the gut-brain axis to mitigate the cognitive and behavioral deficits characteristic of this disorder.”
https://www.sciencedirect.com/science/article/pii/S0753332225009850?via%3Dihub