Berberine directly affects the gut microbiota to promote intestinal farnesoid X receptor activation

Yuan Tian, Jingwei Cai, Wei Gui, Robert G. Nichols, Imhoi Koo, Jingtao Zhang, Mallappa Anitha, Andrew David Patterson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Intestinal bacteria play an important role in bile acid metabolism and in the regulation of multiple host metabolic pathways (e.g., lipid and glucose homeostasis) through modulation of intestinal farnesoid X receptor (FXR) activity. Here, we examined the effect of berberine (BBR), a natural plant alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, the metabolomic response and changes in mouse intestinal bacterial communities treated with BBR (100 mg/kg) for 5 days were assessed using NMR- and mass spectrometry–based metabolomics coupled with multivariate data analysis. Short-term BBR exposure altered intestinal bacteria by reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, which resulted in the accumulation of taurocholic acid (TCA). The accumulation of TCA was associated with activation of intestinal FXR, which can mediate bile acid, lipid, and glucose metabolism. In vitro, isolated mouse cecal bacteria were incubated with three doses of BBR (0.1, 1, and 10 mg/ml) for 4 hours in an anaerobic chamber. NMR-based metabolomics combined with flow cytometry was used to evaluate the direct physiologic and metabolic effect of BBR on the bacteria. In vitro, BBR exposure not only altered bacterial physiology but also changed bacterial community composition and function, especially reducing BSH-expressing bacteria like Clostridium spp. These data suggest that BBR directly affects bacteria to alter bile acid metabolism and activate FXR signaling. These data provide new insights into the link between intestinal bacteria, nuclear receptor signaling, and xenobiotics.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalDrug Metabolism and Disposition
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Berberine
Bacteria
choloylglycine hydrolase
Metabolomics
Bile Acids and Salts
Taurocholic Acid
Clostridium
Bacterial Physiological Phenomena
Glucose
Gastrointestinal Microbiome
Xenobiotics
Cytoplasmic and Nuclear Receptors
Metabolic Networks and Pathways
Lipid Metabolism
Alkaloids
Flow Cytometry
Homeostasis
Multivariate Analysis
Lipids

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Tian, Yuan ; Cai, Jingwei ; Gui, Wei ; Nichols, Robert G. ; Koo, Imhoi ; Zhang, Jingtao ; Anitha, Mallappa ; Patterson, Andrew David. / Berberine directly affects the gut microbiota to promote intestinal farnesoid X receptor activation. In: Drug Metabolism and Disposition. 2019 ; Vol. 47, No. 2. pp. 86-93.
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Berberine directly affects the gut microbiota to promote intestinal farnesoid X receptor activation. / Tian, Yuan; Cai, Jingwei; Gui, Wei; Nichols, Robert G.; Koo, Imhoi; Zhang, Jingtao; Anitha, Mallappa; Patterson, Andrew David.

In: Drug Metabolism and Disposition, Vol. 47, No. 2, 01.02.2019, p. 86-93.

Research output: Contribution to journalArticle

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AU - Cai, Jingwei

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