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Journal of Translational Medicine

, 14:237

Cardiovascular, Metabolic andLipoprotein Translation


BackgroundHyperlipidemia 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.

MethodsMale 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.

ResultsLipid 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.

ConclusionsThe 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.

KeywordsBerberine compounds Integrative metabolomics Gut microbiota Hyperlipidemia AbbreviationsALTalanine aminotransferase

ANOVAanalysis of variance

ASTaspartate aminotransferase


BCberberine compounds

BCAAbranched chain amino acid


CMC-Nasodium carboxy methylcellulose


FCfold change

FFAsfree fatty acids

GC-MSgas chromatography-mass spectrometry

HDL-chigh-density lipoprotein cholesterol

HFDhigh fat diet

InsRinsulin receptor


LDL-clow-density lipoprotein cholesterol

LDLRlow-density lipoprotein receptor

MSRMiSeq reporter software

NMDSnonmetric multidimensional scaling

ODCornithine decarboxylase

OPLS-DAorthogonal partial least squares-discriminant analysis

OTUoperational taxonomic unit

PCAprincipal component analysis

PCoAprincipal coordinate analysis

PLPpyridoxal 5′-phosphate

PLS-DApartial least squares-discriminant analysis

RDPribosomal database project

RSBresuspension buffer


TBAtotal bile acid

TBILtotal bilirubin

TCtotal cholesterol



Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-0987-5 contains supplementary material, which is available to authorized users.

Autor: Meng Li - Xiangbing Shu - Hanchen Xu - Chunlei Zhang - Lili Yang - Li Zhang - Guang Ji


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