Dietary sulforaphane glucosinolate mitigates depression-like behaviors in mice with hepatic ischemia/reperfusion injury: A role of the gut-liver-brain axis

Nutrition has been increasingly recognized for its use in mental health. Depression is commonly observed in patients with chronic liver disease (CLD). Building on our recent findings of depression-like behaviors in mice with hepatic ischemia/reperfusion (HI/R) injury, mediated by the gut-liver-brain axis, this study explored the potential influence of dietary sulforaphane glucosinolate (SGS) on these behaviors. Behavioral assessments for depression-like behaviors were conducted 7 days post either sham or HI/R injury surgery. Dietary intake of SGS significantly prevented splenomegaly, systemic inflammation, depression-like behaviors, and downregulation of synaptic proteins in the prefrontal cortex (PFC) of HI/R-injured mice. Through 16S rRNA analysis and untargeted metabolomic analyses, distinct bacterial profiles and metabolites were identified between control + HI/R group and SGS + HI/R group. Correlations were observed between the relative abundance of gut microbiota and both behavioral outcomes and blood metabolites. These findings suggest that SGS intake could mitigate depressionlike phenotypes in mice with HI/R injury, potentially through the gut-liver-brain axis. Additionally, SGS, found in crucial vegetables like broccoli, could offer prophylactic nutritional benefits for depression in patients with CLD.