Berberine treatment reduces atherosclerosis by mediating gut microbiota in apoE-/- mice

Background: Berberine (BBR) has long been used for treating bacterial diarrhea due to its antimicrobial effect and is currently used to treat obesity, diabetes, hyperlipemia and atherosclerosis. Given the poor oral bioavailability of BBR, the mechanisms through which BBR mediates metabolic disorders are not well understood. The present study was designed to explore the role of BBR-induced gut microbiota modulation in the development of atherosclerosis. Methods: Male apoE-/- mice were fed a high-fat diet (HFD) with or without the intragastric administration of BBR. Because mice are coprophagic and can transfer their gut microbiota to each other, we cohoused BBR-treated HFD-mice with non-BBR-treated HFD-fed mice. Results: After 12 weeks of HFD feeding, compared with non-BBR-treated HFD-fed mice, BBR-treated HFD-fed mice exhibited a significant reduction in both atherosclerosis development and inflammatory cytokine expression. In addition, cohousing BBR-treated HFD-fed mice with non-BBR-treated HFD-fed mice decreased atherosclerosis development and inflammatory cytokine expression. The denaturing gradient gel electrophoresis and principal component analyses showed that the gut microbial profiles of BBR-treated HFD-fed mice were significantly different from those of HFD-fed mice but were similar to those of cohoused mice. The abundances of Firmicutes and Verrucomicrobia in cohoused and BBR-treated mice were different from those in HFD-fed and normal chow-fed mice. Moreover, BBR reduced hepatic FMO3 expression and serum trimethylamine N-oxide levels. Conclusion: The antiatherosclerotic effect of BBR is related to alterations in gut microbiota compositions, indicating the potential therapeutic value of pharmacological approaches that may modulate the gut microbiota in treating atherosclerosis.