ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Pharmacological Activation of PXR and CAR Downregulates Distinct Bile Acid-Metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- The gut microbiome-bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases.Gut microbes · 2026Review
- Role of Bile Acid Receptors in Non-Infectious Diarrhea: A Narrative Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Effects of Supplementing Yeast Culture to Prepartum Cows Under Heat Stress on the Jejunal Microbiota and Metabolites of Calves.Animals : an open access journal from MDPI · 2026Article
- Expansion resistance against genotoxicFrontiers in microbiology · 2026Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- The hypolipidemic effect of MI-883, the combined CAR agonist/ PXR antagonist, in diet-induced hypercholesterolemia model.Nature communications · 2025Article
- Synthesis of TUDCA from chicken bile: immobilized dual-enzymatic system for producing artificial bear bile substitute.Microbial cell factories · 2024Review
- Lactobacillus gasseri ATCC33323 affects the intestinal mucosal barrier to ameliorate DSS-induced colitis through the NR1I3-mediated regulation of E-cadherin.PLoS pathogens · 2024Article
- Association between gut microbiota and hepatocellular carcinoma and biliary tract cancer: A mendelian randomization study.World journal of clinical cases · 2024Article
- The Supplementation of Berberine in High-Carbohydrate Diets Improves Glucose Metabolism of Tilapia (Animals : an open access journal from MDPI · 2024Article
- Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives.Frontiers in pharmacology · 2024Review
- Bile Acid and Gut Microbiota in Irritable Bowel Syndrome.Journal of neurogastroenterology and motility · 2022Review
- Multi-Omics Strategies for Investigating the Microbiome in Toxicology Research.Toxicological sciences : an official journal of the Society of Toxicology · 2022Review
- Pharmacometabonomic association of cyclophosphamide 4-hydroxylation in hematopoietic cell transplant recipients.Clinical and translational science · 2022Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice.Acta pharmaceutica Sinica. B · 2022Article
- Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Pegbelfermin selectively reduces secondary bile acid concentrations in patients with non-alcoholic steatohepatitis.JHEP reports : innovation in hepatology · 2022Article
- Chronic exposure to ambient traffic-related air pollution (TRAP) alters gut microbial abundance and bile acid metabolism in a transgenic rat model of Alzheimer's disease.Toxicology reports · 2022Article
- Cadmium exposure modulates the gut-liver axis in an Alzheimer's disease mouse model.Communications biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The gut microbiome regulates important host metabolic pathways including xenobiotic metabolism and intermediary metabolism, such as the conversion of primary bile acids (BAs) into secondary BAs. The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known regulators for xenobiotic biotransformation in liver. However, little is known regarding the potential effects of PXR and CAR on the composition and function of the gut microbiome. To test our hypothesis that activation of PXR and CAR regulates gut microbiota and secondary BA synthesis, 9-week-old male conventional and germ-free mice were orally gavaged with corn oil, PXR agonist PCN (75 mg/kg), or CAR agonist TCPOBOP (3 mg/kg) once daily for 4 days. PCN and TCPOBOP decreased two taxa in the Bifidobacterium genus, which corresponded with decreased gene abundance of the BA-deconjugating enzyme bile salt hydrolase. In liver and small intestinal content of germ-free mice, there was a TCPOBOP-mediated increase in total, primary, and conjugated BAs corresponding with increased Cyp7a1 mRNA. Bifidobacterium, Dorea, Peptociccaceae, Anaeroplasma, and Ruminococcus positively correlated with T-UDCA in LIC, but negatively correlated with T-CDCA in serum. In conclusion, PXR and CAR activation downregulates BA-metabolizing bacteria in the intestine and modulates BA homeostasis in a gut microbiota-dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.