Nuciferine modulates the gut microbiota and prevents obesity in high-fat diet-fed rats

Gut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity. Obesity: Getting leaner on lotus leaves A natural compound found in lotus leaf could treat and prevent obesity by stabilizing disrupted gut microbiota and reducing the associated chronic. Obesity is a considerable health burden worldwide, yet treatment options are limited. The composition of an individual's gut microbiota influences the development of obesity; an imbalance in the ratio of two bacterial species in particular can accelerate the disease. Mingyan Liu and Minjie Wei at the China Medical University, Shenyang, and co-workers demonstrated that nuciferine, a bioactive component of lotus leaf, reduced weight gain and fat accumulation in rats fed a high-fat diet. Nuciferine changed the diversity and composition of the rats' gut microbiota, and modified the expression of genes involved in processes such as lipid metabolism. Nuciferine also enhanced intestinal integrity, and reduced chronic low-level inflammation.