OBJECTIVE To investigate the regulatory effects of Trichosanthes kirilowii root resistant starch-carboxymethyl chitosan complex (TKR-RS-CMC) on lipid metabolism and intestinal flora in obese mice by adding it to their diet.

METHODS The TKR-RS-CMC was premix-mixed with basic diet and fed to Lepob/ob mice. The changes of body weight and blood glucose were observed, liver weight was determined, and pathological status of liver in each group was analyzed. Serum triglyceride (TG), total cholesterol (TC), insulin (INS), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT), malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue were detected by biochemical and ELISA. Mice colon contents were sequenced with 16S rDNA in high throughput, and mice serum was analyzed by UPLC-Q-TOF/MS.

RESULTS Lepob/ob model mice showed dyslipidemia, which was represented by increased contents of TC, TG and LDL-C (P < 0.001) and decreased content of HDL-C (P < 0.001). TKR-RS-CMC could significantly improve the dyslipidemia by reducing the contents of TC and LDL-C (P < 0.001) and increasing the content of HDL-C (P < 0.001) in obese mice. Lepob/ob model mice showed disorder of oxygen free radical metabolism, which was represented by decreased SOD activity (P < 0.001) and increased MDA content (P < 0.001), and MDA content decreased significantly (P < 0.001) after TKR-RS-CMC was given in the diet. The results of oil red O staining and HE staining showed that the liver of Lepob/ob model mice had pathological changes, and the liver pathological sections of the administration group showed that the degree of damage was reduced. Obesity led to intestinal flora disorder, in which the relative abundance of Prevotellaceae_UCG-001 was significantly reduced (P < 0.01), and the relative abundance of the above flora was reversed to that of the control group after TKR-RS-CMC was given in the diet. Compared with the model group, the relative abundance of Erysipelatoclostridium in the TKR-RS-CMC high-dose group was significantly decreased (P < 0.05), while the relative abundance of Akkermansia, Muribaculum, Bifidobacterium and Ileibacterium was significantly increased (P < 0.05). TKR-RS-CMC could significantly regulate the disregulated fatty acids and phospholipids in the serum of obese mice, involving the glycero phospholipid metabolic pathway, the mutual conversion pathway between pentose and glucuronic acid, and the metabolic pathway of cysteine and methionine. Spearman correlation analysis showed that metabolites involved in glycero phospholipid metabolic pathway were significantly associated with different intestinal flora. The probiotic Akkermansia was significantly negatively correlated with LysoPC(P-18∶0/0∶0), LysoPC(P-16∶0/0∶0) and other phospholipid metabolites.

CONCLUSION TKR-RS-CMC can regulate the intestinal flora of obese mice and balance the disorder of blood lipid metabolism, suggesting that the compound could be used as a potential dietary supplement to ameliorate obesity.