EXPLORING NEUROBIOLOGICAL FACTORS UNDERLYING RISK AND RESILIENCY FOR EMOTIONAL DYSREGULATION AND THE THERAPEUTIC POTENTIAL OF FECAL MICROBIOTA TRANSPLANTATION IN ANIMALS PRENATALLY EXPOSED TO ALCOHOL

Prenatal alcohol exposure (PAE) induces emotional dysregulation, yet not all individuals are affected, suggesting the presence of neurobiological factors that confer resilience. Because gut microbiota-immune system interactions can regulate emotionality, here we explored if alterations within this system may contribute to risk for, or resilience against, emotional dysregulation following PAE. As fecal microbiota transplantation (FMT) improves emotional dysregulation, we also evaluated the therapeutic potential of FMT to improve emotional regulation in PAE. Emotional regulation of adult male and female PAE and control offspring was assessed using the open field, dark-light, social interaction, and sucrose preference. Scores from behavioral individual tasks were compiled into a single emotionality score and 10 animals in each group with the highest (risk) and lowest (resilience) scores were selected for assessment of gut microbiota (16S rRNA sequencing of fecal samples) and immune function (cytokine levels in serum and brain). PAE animals exhibited higher emotionality scores indicating greater risk and less resiliency for emotional dysregulation. PAE animals classified as risk exhibited sex-specific alterations in specific bacterial taxa, and in pro- and anti-inflammatory cytokines across specific limbic regions. Separately, gut-depleted PAE and control animals received FMT from either control donors, PAE donors, or a sham treatment for 3-days during adolescence and assessed for anxiety-and depressive-like behaviors, and for alterations in the gut microbiota during adulthood. While FMT from control donors improves sucrose preference in males, overall, this treatment was unable to ameliorate PAE-induced anxiety- and depressive-like behaviors. Support: NIH/NIAAA R01 AA022460 and Azrieli Foundation to CR and TSB.