ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Regulation of Hepatic Drug-Metabolizing Enzymes in Germ-Free Mice by Conventionalization and Probiotics.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 131 citations in OpenAlex.
- The microbiota at the interface of environmental toxicants and the brain.Cell metabolism · 2026Review
- Bacillus velezensis mitigates deoxynivalenol-induced intestinal inflammation and liver injury via modulating the gut microbiota.NPJ science of food · 2026Article
- Novel Approaches in Establishing Chemical Food Safety Based on the Detoxification Capacity of Probiotics and Postbiotics: A Critical Review.Probiotics and antimicrobial proteins · 2026Review
- Probiotic pretreatment reduced the florfenicol concentration and shortened the withdrawal time in Asian seabass (Lates calcarifer) presumably by decreasing drug absorption.Fish physiology and biochemistry · 2025Article
- Epigenetics and Gut Microbiota in the Pathogenesis and Treatment of Bipolar Disorder (BD).Cells · 2025Review
- Circadian Disruption and Sleep Disorders in Astronauts: A Review of Multi-Disciplinary Interventions for Long-Duration Space Missions.International journal of molecular sciences · 2025Review
- Phenoconversion andHepatology forum · 2025Review
- The microbiome and lung cancer: microbial effects on host immune responses and treatment outcomes.Frontiers in microbiomes · 2025Review
- Article
- Integrating the gut microbiome and pharmacology.Science translational medicine · 2024Review
- Obesity, dysbiosis and inflammation: interactions that modulate the efficacy of immunotherapy.Frontiers in immunology · 2024Review
- Antibiotics affect the pharmacokinetics of n-butylphthalide in vivo by altering the intestinal microbiota.PloS one · 2024Article
- Commensal microbiota regulate renal gene expression in a sex-specific manner.American journal of physiology. Renal physiology · 2023Article
- The PPARα/CYP4A14 bile acid pathway is associated with lipid metabolism disorders caused by low birth weight with high-fat diet.Food & nutrition research · 2023Article
- Assessing the role of the gut microbiome at the interface between environmental chemical exposures and human health: Current knowledge and challenges.Environmental pollution (Barking, Essex : 1987) · 2022Review
- Microbiota analysis for risk assessment of xenobiotics: toxicomicrobiomics, incorporating the gut microbiome in the risk assessment of xenobiotics and identifying beneficial components for One Health.EFSA journal. European Food Safety Authority · 2022Article
- Effect of gut microbiota on colorectal cancer progression and treatment.Saudi medical journal · 2022Article
- Role and Regulation of Hepatobiliary ATP-Binding Cassette Transporters during Chemical-Induced Liver Injury.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Effect of DSS-Induced Ulcerative Colitis and Butyrate on the Cytochrome P450 2A5: Contribution of the Microbiome.International journal of molecular sciences · 2022Article
- Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia.Cell death & disease · 2022Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Little is known regarding the effect of intestinal microbiota modifiers, such as probiotics and conventionalization with exogenous bacteria, on host hepatic drug metabolism. Therefore, the goal of this study was to determine the effect of these modifiers on the expression of various drug-metabolizing enzymes of the host liver. VSL3 is a probiotic that contains eight live strains of bacteria. Five groups of mice were used: 1) conventional mice (CV), 2) conventional mice treated with VSL3 in drinking water, 3) germ-free (GF) mice, 4) GF mice treated with VSL3, and 5) GF mice exposed to the conventional environment for 2 months. All mice were 3 months old at tissue collection. GF conditions markedly downregulated the cytochrome P450 (P450) 3a gene cluster, but upregulated the Cyp4a cluster, whereas conventionalization normalized their expression to conventional levels [reverse-transcription quantitative polymerase chain reaction (qPCR) and western blot]. Changes in the Cyp3a and 4a gene expression correlated with alterations in the pregnane X receptor and peroxisome proliferator-activated receptor α-DNA binding, respectively (chromatin immunoprecipitation-qPCR). VSL3 increased each bacterial component in the large intestinal content of the CV mice, and increased these bacteria even more in GF mice, likely due to less competition for growth in the GF environment. VSL3 given to conventional mice increased the mRNAs of Cyp4v3, alcohol dehydrogenase 1, and carboxyesterase 2a, but decreased the mRNAs of multiple phase II glutathione-S-transferases. VSL3 given to germ-free mice decreased the mRNAs of UDP-glucuronosyltransferases 1a9 and 2a3. In conclusion, conventionalization and VSL3 alter the expression of many drug-metabolizing enzyme s in the liver, suggesting the importance of considering "bacteria-drug" interactions for various adverse drug reactions in patients.
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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.