Dose-response effect of berberine on bile acid profile and gut microbiota in mice.

Ying Guo,Youcai Zhang,Curtis D Klaassen,Weihua Huang,Felcy Pavithra Selwyn

doi:10.1186/s12906-016-1367-7

Abstract

BackgroundBerberine (BBR) is a traditional antimicrobial herbal medicine. Recently, BBR has gained popularity as a supplement to lower blood lipids, cholesterol and glucose. Bile acids (BAs) are known to regulate blood levels of triglycerides, cholesterol, glucose and energy homeostasis, and gut flora play an important role in BA metabolism. However, whether BBR alters BAs metabolism or dose-response effect of BBR on gut flora is unknown.MethodsIn this study, the effects of various doses of BBR on the concentrations of BAs in liver and serum of male C57BL/6 mice were determined by UPLC-MS/MS, and the expression of BA-related genes, as well as the amount of 32 of the most abundant gut bacterial species in the terminal ileum and large intestine of male C57BL/6 mice were quantified by RT-PCR and Quantigene 2.0 Reagent System, respectively.ResultsUnconjugated BAs and total BAs were significantly altered by BBR in serum but not in liver. Increased primary BAs (βMCA, TβMCA and TUDCA) and decreased secondary BAs (DCA, LCA and the T-conjugates) were observed in livers and serum of mice fed BBR. The expression of BA-synthetic enzymes (Cyp7a1 and 8b1) and uptake transporter (Ntcp) increased 39-400 % in liver of mice fed the higher doses of BBR, whereas nuclear receptors and efflux transporters were not markedly altered. In addition, Bacteroides were enriched in the terminal ileum and large bowel of mice treated with BBR.ConclusionThe present study indicated that various doses of BBR have effects on BA metabolism and related genes as well as intestinal flora, which provides insight into many pathways of BBR effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1367-7) contains supplementary material, which is available to authorized users.

Highlights

IntroductionBBR has gained popularity as a supplement to lower blood lipids, cholesterol and glucose
Berberine (BBR) is a traditional antimicrobial herbal medicine
Concentrations of T-conjugated Bile acid (BA), unconjugated BAs and total BAs in livers and serum of control and BBR-treated mice The T-conjugated BAs and total BAs did not change significantly in livers of the BBR-treated mice (Fig. 2a), in serum, the unconjugated BAs significantly increased (P = 0.0017) about 90–92 % at the two middle doses of BBR (10 and 30 mg/kg) while they tended to decrease after the highest dose

Summary

Introduction

BBR has gained popularity as a supplement to lower blood lipids, cholesterol and glucose. Bile acids (BAs) are known to regulate blood levels of triglycerides, cholesterol, glucose and energy homeostasis, and gut flora play an important role in BA metabolism. Bile acids (BAs) are important natural detergents that form micelles to facilitate the absorption of dietary fat and lipid soluble vitamins from the gastrointestinal tract. BAs are important metabolic and inflammatory signaling molecules as they regulate lipid- and energy-related nuclear hormone receptors, such as farnesoid-X-receptor (FXR) and transmembrane G-proteincoupled receptor 5 (TGR5 or GPBAR1) [2, 3]. Primary BAs are synthesized in the liver and are converted to secondary BAs by bacteria in the intestine. The liver synthesizes primary BAs, namely cholic acid (CA) and chenodeoxycholic acid (CDCA) from cholesterol. A portion of the BAs are directly effluxed into the blood by the efflux transporters on the

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