Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.