Berberine alters gut microbial function through modulation of bile acids.
Animals
Bacteria
/ classification
Bacterial Proteins
/ genetics
Berberine
/ administration & dosage
Bile Acids and Salts
/ metabolism
DNA, Bacterial
/ genetics
DNA, Ribosomal
/ genetics
Female
Gastrointestinal Microbiome
/ drug effects
Gene Expression Profiling
Gene Expression Regulation, Bacterial
/ drug effects
Male
Metabolomics
Mice
RNA, Ribosomal, 16S
/ genetics
Sequence Analysis, RNA
Species Specificity
Berberine
Bile acids
Gnotobiotic mice
Gut bacteria
Network analysis
Nutraceutical
RNA-Seq
Journal
BMC microbiology
ISSN: 1471-2180
Titre abrégé: BMC Microbiol
Pays: England
ID NLM: 100966981
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
received:
09
06
2020
accepted:
26
10
2020
entrez:
12
1
2021
pubmed:
13
1
2021
medline:
30
10
2021
Statut:
epublish
Résumé
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. 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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 33430766
doi: 10.1186/s12866-020-02020-1
pii: 10.1186/s12866-020-02020-1
pmc: PMC7798349
doi:
Substances chimiques
Bacterial Proteins
0
Bile Acids and Salts
0
DNA, Bacterial
0
DNA, Ribosomal
0
RNA, Ribosomal, 16S
0
Berberine
0I8Y3P32UF
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24Subventions
Organisme : NCI NIH HHS
ID : R01 CA179243
Pays : United States
Organisme : Department of Animal Sciences, University of Illinois at Urbana-Champaign (US)
ID : Hatch ILLU-538-916
Organisme : Foundation for the National Institutes of Health
ID : 1RO1 CA204808-01
Organisme : University of Illinois
ID : RB18068
Organisme : NIDDK NIH HHS
ID : R01 DK114007
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA057699
Pays : United States
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