Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse...

Growing evidence supports the pivotal role of the bidirectional interplay between the gut microbiota and the central nervous system during the progression of alcohol use disorder (AUD). In our previous study, supplementation with sodium butyrate (SB) in C57BL/6J mice prevented increased ethanol consumption in a binge-like drinking paradigm (DID) as a result of treatment with a non-absorbable antibiotic cocktail (ABX). In this study, we tested the hypothesis that SB protection against enhanced ABX-induced ethanol consumption in mice is partially due to modulation of neuroinflammatory responses. Pro- and anti-inflammatory cytokines, as well as changes in microglia and astrocytes were analyzed in hippocampus tissues from ABX-, SB-, ABX+SB-treated mice subjected to 4-week DID. We found that ethanol without or with ABX treatment increased mRNA levels of key brain cytokines (MCP-1, TNF-α, IL-1β, IL-6 and IL-10) while SB supplementation prevented these changes. Additionally, SB supplementation prevented changes in microglia, i.e., increase in Iba-1 positive cell number and morphology, and in astrocytes, i.e., decrease in GFAP-positive cell number, induced by combination of ethanol and ABX treatments. Our results suggest that gut microbiota metabolites can influence drinking behavior by modulation of neuroinflammation, highlighting the potential for microbiome-targeting strategies for treatment or prevention of AUD.