Role of gut microbiota and its functional products in prenatal alcohol-induced anxiety-like behavior.

Prenatal alcohol exposure (PAE) has been shown to increase vulnerability to anxiety. Alterations in the gut microbiota and its functional products (i.e., short-chain fatty acids, SCFAs) are a potential mechanism underlying anxiety behaviors induced by PAE. Here, we used a rat model of PAE to examine the impact of alcohol consumption during gestation on anxiety-like behaviors, gut microbiota, and SCFA levels in adult male and female offspring. PAE male and female rats exhibited increased anxiety-like behavior on the open field test; moreover, control animals displayed striking sex differences in the light-dark test, but sex differences were attenuated among PAE males and females. Furthermore, using an anxiety index composed of open field and light-dark behaviors, we showed that PAE animals had higher anxiety scores compared to controls. PAE did not affect bacterial diversity and community structure; however, in males, PAE reduced the abundance of the Firmicutes phylum, increased the abundance of the Bacteroidota phylum, and decreased the abundance of the Lachnospiraceae NK4A136 group genus compared to controls. In females, PAE increased abundance of Turicibacter genus compared to controls. PAE did not affect fecal SCFA levels; however, lower levels of butyric and valeric acid were associated with higher anxiety among PAE females. This study identified several bacterial taxa and SCFAs potentially involved in the mechanisms through which PAE induces anxiety-like behaviors. These findings also underscore the importance of considering sex differences when assessing anxiety-like behavior and gut microbiota to identify potential biomarkers for interventions targeting mental health issues in individuals with PAE.