Maternal gut and vaginal microbiota, alcohol use during pregnancy, and infant fetal alcohol spectrum disorder diagnosis in a South African cohort

<jats:p> <jats:bold>Background</jats:bold> The detrimental impact of alcohol consumption on the gut microbiome is well-established. However, less is known about how alcohol exposure during pregnancy affects the maternal gut and vaginal microbiota, or how these microbial changes relate to subsequent infant diagnosis of fetal alcohol spectrum disorder (FASD). We therefore investigated associations between self-reported alcohol use during pregnancy, infant FASD diagnosis, and maternal gut and vaginal microbiota. <jats:bold>Methods</jats:bold> Fecal samples (n = 207) and vaginal swabs (n = 28) from pregnant participants recruited through antenatal clinics in the Western Cape Province of South Africa were profiled by 16S rRNA V1-V2 amplicon sequencing. Maternal alcohol use was assessed using Alcohol Use Disorder Identification Test (AUDIT) scores, and FASD was diagnosed in infants using revised Institute of Medicine criteria. Microbial diversity, taxonomic profiles and <jats:italic>PICRUSt2</jats:italic> -predicted functional pathways were analyzed using <jats:italic>vegan</jats:italic> , <jats:italic>phyloseq</jats:italic> and <jats:italic>MaAsLin3</jats:italic> . <jats:bold>Results</jats:bold> Maternal AUDIT scores were negatively associated with maternal gut microbiota richness, Shannon, and Inverse Simpson diversity (p &lt; 0.05). Observed richness was also reduced in participants whose infants were diagnosed with FASD (p = 0.046). Gut microbiota community structure was not significantly associated with alcohol use or infant FASD diagnosis. However, taxonomic and functional analysis suggested gram-positive taxa depletion with alcohol use and FASD diagnosis, and impaired one-carbon metabolism among participants with infants diagnosed with FASD. Vaginal microbiota diversity and composition were not associated with alcohol use or infant diagnosis. <jats:bold>Conclusions</jats:bold> This is the first human study to investigate the maternal gut and vaginal microbiota in relation to alcohol use during pregnancy and infant FASD outcomes. Our findings suggest that alcohol use is associated with maternal gut microbiota disruption, with potential implications for FASD development in exposed infants. Further investigation of alcohol-associated maternal microbial disturbances may inform microbiota-targeted strategies to improve maternal and infant health linked to alcohol use. </jats:p>