Berberine alters gut microbial function through modulation of bile acids

BMC Microbiology

Tyler Moore¹  Heidi L. Doden²  Saravanan Devendran²  Lindsey K. Ly²  Jason M. Ridlon²  H. Rex Gaskins²  Vance J. McCracken³  Genta Kakiyama⁴  Purna Kashyap⁵  Patricia G. Wolf⁶  Hajime Takei⁷  Hiroshi Nittono⁷  Tsuyoshi Murai⁸  Takao Kurosawa⁸  Patrick M. Gillevet⁹  George E. Chlipala^1,10  Stefan J. Green^1,10 

[1] Center for Microbiome Analysis, George Mason University;Department of Animal Sciences, University of Illinois Urbana-Champaign;Department of Biological Sciences, Southern Illinois University Edwardsville;Department of Internal Medicine, School of Medicine, Virginia Commonwealth University;Department of Internal Medicine;Institute for Health Research and Policy, University of Illinois Chicago;Junshin Clinic Bile Acid Institute;School of Pharmaceutical Sciences, Health Sciences University of Hokkaido;Structural and Computational Biology Research Unit, European Molecular Biology Laboratory;University of Illinois Chicago Research Resources Center, University of Illinois Chicago;

关键词: Berberine;    Bile acids;    Gnotobiotic mice;    Gut bacteria;    Network analysis;    Nutraceutical;   

DOI  :  10.1186/s12866-020-02020-1

来源: DOAJ

【 摘 要 】

Abstract Background Berberine (BBR) is a plant-based nutraceutical that has been used for millennia to treat diarrheal infections and in contemporary medicine to improve patient lipid profiles. Reduction in lipids, particularly cholesterol, is achieved partly through up-regulation of bile acid synthesis and excretion into the gastrointestinal tract (GI). The efficacy of BBR is also thought to be dependent on structural and functional alterations of the gut microbiome. However, knowledge of the effects of BBR on gut microbiome communities is currently lacking. Distinguishing indirect effects of BBR on bacteria through altered bile acid profiles is particularly important in understanding how dietary nutraceuticals alter the microbiome. Results Germfree mice were colonized with a defined minimal gut bacterial consortium capable of functional bile acid metabolism (Bacteroides vulgatus, Bacteroides uniformis, Parabacteroides distasonis, Bilophila wadsworthia, Clostridium hylemonae, Clostridium hiranonis, Blautia producta; B4PC2). Multi-omics (bile acid metabolomics, 16S rDNA sequencing, cecal metatranscriptomics) were performed in order to provide a simple in vivo model from which to identify network-based correlations between bile acids and bacterial transcripts in the presence and absence of dietary BBR. Significant alterations in network topology and connectivity in function were observed, despite similarity in gut microbial alpha diversity (P = 0.30) and beta-diversity (P = 0.123) between control and BBR treatment. BBR increased cecal bile acid concentrations, (P < 0.05), most notably deoxycholic acid (DCA) (P < 0.001). Overall, analysis of transcriptomes and correlation networks indicates both bacterial species-specific responses to BBR, as well as functional commonalities among species, such as up-regulation of Na+/H+ antiporter, cell wall synthesis/repair, carbohydrate metabolism and amino acid metabolism. Bile acid concentrations in the GI tract increased significantly during BBR treatment and developed extensive correlation networks with expressed genes in the B4PC2 community. Conclusions This work has important implications for interpreting the effects of BBR on structure and function of the complex gut microbiome, which may lead to targeted pharmaceutical interventions aimed to achieve the positive physiological effects previously observed with BBR supplementation.

【 授权许可】

Unknown