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

Abstract

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.

HMB Improves Lipid Metabolism of Bama Xiang Mini-Pigs via Modulating the Bacteroidetes-Acetic Acid-AMPKα Axis

“…The metabolic activity of the gut microbiota can be linked to host body energy homoeostasis by short-chain fatty acids (SCFAs), which are produced by gut microbiota catabolizing dietary fibers (Topping and Clifton, 2001). There is compelling evidence that nutrients can attenuate obesity by reprogramming gut microbiota (Xu et al, 2017;Yin et al, 2018;Zhang et al, 2019;Wang et al, 2020;Zhong et al, 2020). Using a rodent model, we also found that HMB could mitigate lipid metabolism disorders by reprogramming gut microbiota, as manifested by the increased ratio of Bacteroidetes to Firmicutes and elevated Bacteroidetesproduced propionic acid (Duan et al, 2019).…”

Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

“…Nuciferine in lotus extracts is absorbed by the intestinal tract, showing a low permeability under a multi-component environment [ 81 , 82 ]. Nuciferine supplementation can prevent weight gain, reduce fat accumulation, and ameliorate lipid metabolic disorder in high-fat diet-fed rats [ 83 ]. Antibiotics substantially abolish the beneficial anti-hyperlipidemic and anti-liver steatosis effects of nuciferine.…”

“…Antibiotics substantially abolish the beneficial anti-hyperlipidemic and anti-liver steatosis effects of nuciferine. 16S rRNA gene sequencing of fecal microbiota further shows that nuciferine also modulates gut microbiota dysbiosis and changes the diversity and composition of gut microbiota towards a healthy level in high-fat diet-fed rats [ 83 ]. The data from the composition of gut microbiota show that nuciferine significantly shifts microbial structure, which includes the reduction in the abundance of Butyricimonas and the enhancement of the abundance of Akkermansia, an anti-obesity bacterium in high-fat diet-fed animals [ 84 , 85 ].…”

Supplementation of Kiwifruit Polyphenol Extract Attenuates High Fat Diet Induced Intestinal Barrier Damage and Inflammation via Reshaping Gut Microbiome

“…Numerous environmental factors may regulate tight junction protein and intestinal permeability, such as luminal microbiota, pro-inflammatory mediators and dietary component (3,4). High fat diet (HFD) induced obesity increased intestinal permeability came from animal models (5)(6)(7). The increased intestinal permeability was correlated with disrupted composition of gut microbiota (8).…”