Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.

The gut microbiota, identified as the target for vegetables, can affect the development of obesity and associated metabolic syndromes. As a medicinal and edible plant, Luffa cylindrica (L.) Roem (LC) has abundant nutrients that can effectively reduce obesity risk. However, the interaction between the prevention effects of LC against obesity and the modulating gut microbiota of LC remain obscure. This study demonstrated LC supplementation improved high-fat diet (HFD)-induced gut microbiota dysbiosis and significantly enhanced short-chain fatty acid (SCFA)-producing bacteria (e.g., Blautia) along with SCFA content accumulation in the gut. Meanwhile, LC supplementation substantially restored gut barrier damage in long-term HFD treatment. Moreover, LC supplementation improved HFD-induced overweight, hyperlipidemia, insulin resistance, and chronic inflammation. Gene expression profiles showed that LC displayed an important impact on hepatic lipid transport and lipid synthesis (sterol regulatory element binding transcriptional factor 1c-peroxisome proliferator-activated receptor γ signaling pathway). More importantly, an antibiotic treatment experiment demonstrated that the beneficial effects of LC in reducing obesity risk largely depended on the gut microbiota, especially SCFA-producing bacteria (e.g., Blautia). Therefore, LC supplementation improved gut microbiota dysbiosis via enhancing SCFA-producing bacteria (e.g., Blautia), maintained gut barrier integrity, and alleviated the development of obesity. Overall, LC would provide a potential dietary intervention strategy against obesity and enteral homeostasis dysbiosis through modulating the gut microbiota.-Zhang, L., Shi, M., Ji, J., Hu, X., Chen, F. Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.