UC San Diego

Alcohol Use Disorder (AUD) is a significant public health concern, with alcohol-related deaths accounting for approximately 178,000 deaths nationwide and increasing in recent years (White et al., 2022). To better understand the role of the gut microbiome in AUD, a chronic intermittent ethanol (CIE) model was utilized in heterogeneous stock (HS) rats, and gut microbial and metabolic changes were measured.Differential microbiome and metabolomic features were found between sexes, dependence timepoints, addiction levels, and pharmaceutical treatment responses. Before alcohol dependence, high-addiction females had significantly lower Tenericutes levels than low-addiction females, suggesting a predictive capability of Tenericutes in addiction for females. After dependence, high-addiction rats had higher SR1 abundances than low-addiction rats. Rats responding well to naltrexone treatment had higher abundances of Verrucomicrobia, Fusobacteria, and SR1. Metabolomic analysis revealed differential levels of linoleic acid between vulnerable and resistant rats at baseline. These differences were hypothesized to be linked to variations in catechol-O-methyltransferase (COMT) activity, an enzyme involved in the degradation of catecholamines associated with addiction (Coker et al., 2020a; Schacht et al., 2022a). A COMT inhibitor was tested in alcohol-dependent rats with promising results. The results demonstrate that microbial abundance levels can predict addiction-like behaviors in females and response to treatment drugs. Further research on microbial differences between different types of medication could provide valuable insights for optimizing AUD treatment strategies.