Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds

• Published in: Journal of translational medicine 2016-08, Vol.14 (1), p.237-237, Article 237
• Main Authors: Li, Meng, Shu, Xiangbing, Xu, Hanchen, Zhang, Chunlei, Yang, Lili, Zhang, Li, Ji, Guang
• Format: Article
• Language: English
• Subjects: Animals; Anticholesteremic agents; Berberine - adverse effects; Berberine - pharmacology; Berberine - therapeutic use; Body Weight - drug effects; Cardiovascular diseases; Care and treatment; Diet, High-Fat; Dosage and administration; Feces - microbiology; Gastrointestinal Microbiome - drug effects; Health aspects; Hyperlipidemia; Hyperlipidemias - blood; Hyperlipidemias - chemically induced; Hyperlipidemias - drug therapy; Hyperlipidemias - metabolism; Liver - drug effects; Liver - pathology; Male; Metabolome - drug effects; Metabolomics - methods; Microbiota (Symbiotic organisms); Organ Size - drug effects; Phenotype; Polyamines; Rats, Wistar; Risk factors
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-016-0987-5

Hyperlipidemia is a major component of metabolic syndrome, and often predicts cardiovascular diseases. We developed a new therapeutic agent berberine compounds (BC), consisting of berberine, oryzanol and vitamin B6, and determined their anti-hyperlipidemia activity and underlying mechanisms. Male Wistar rats were fed a high fat diet (HFD) to induce hyperlipidemia, and then given BC orally for 4 weeks. Body weight and food intake were recorded weekly, and lipid profiles in serum were determined biochemically. Metabolites in serum, urine, liver and feces were analyzed by GC-MS, and the structure of microbiota was determined by 16S rDNA sequencing. Lipid lowering was observed in the hyperlipidemic rats upon BC treatment without apparent adverse side effects. Metabolomics analysis indicated that the BC treatment resulted in increased pyruvic acid, serotonin, and ketogenic and glycogenic amino acid levels in the serum, increased pyridoxine and 4-pyridoxic acid in the urine, decreased hypotaurine and methionine in the liver, and increased putrescine and decreased deoxycholate and lithocholate in feces. The BC treatment also resulted in an enrichment of beneficial bacteria (e.g. Bacteroides, Blautia) and a decrease in Escherichia. The lipid lowering effect of BC treatment in hyperlipidemic rats is associated with a global change in the metabolism of lipids, carbohydrates and amino acids, as well as the structure of microbiota.