The gut microbiome: an orchestrator of xenobiotic metabolism
| Autor: | Stephanie L. Collins, Andrew D. Patterson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Enterohepatic circulation
BDE bromodiphenyl ether ER estrogen receptor GUDCA glycoursodeoxycholic acid Microbial metabolism PCB polychlorinated biphenyl Review SCFA short chain fatty acid PD Parkinson's disease chemistry.chemical_compound 0302 clinical medicine Gastrointestinal tract NSAID non-steroidal anti-inflammatory drug General Pharmacology Toxicology and Pharmaceutics 0303 health sciences cgr cytochrome glycoside reductase PXR pregnane X receptor BRV brivudine CAR constitutive androgen receptor CV conventional TCDF 2 3 7 8-tetrachlorodibenzofuran Cell biology 030220 oncology & carcinogenesis CYP cytochrome P450 PAH polycyclic aromatic hydrocarbon SULT sulfotransferase SN-38G SN-38 glucuronide Biology BVU bromovinyluracil Absorption 03 medical and health sciences FXR farnesoid X receptor TUDCA tauroursodeoxycholic acid Detoxification Pharmacokinetics Microbiome Transcription factor 030304 developmental biology Gut microbiome Bioactivation UGT uracil diphosphate-glucuronosyltransferase lcsh:RM1-950 PABA p-aminobenzenesulphonamide PFOS perfluorooctanesulfonic acid Metabolism Xenobiotic metabolism GF germ-free ALDH aldehyde dehydrogenase lcsh:Therapeutics. Pharmacology chemistry 5-ASA 5-aminosalicylic acid AHR aryl Hydrocarbon Receptor 5-FU 5-fluorouracil Xenobiotic Drug metabolism |
| Zdroj: | Acta Pharmaceutica Sinica B, Vol 10, Iss 1, Pp 19-32 (2020) Acta Pharmaceutica Sinica. B |
| ISSN: | 2211-3835 |
| Popis: | Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism. The gut microbiome, the collection of microorganisms in the gastrointestinal tract, can alter the metabolic outcome of pharmaceuticals, environmental toxicants, and heavy metals, thereby changing their pharmacokinetics. Direct chemical modification of xenobiotics by the gut microbiome, either through the intestinal tract or re-entering the gut via enterohepatic circulation, can lead to increased metabolism or bioactivation, depending on the enzymatic activity within the microbial niche. Unique enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification pathways. Additionally, the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell–cell adhesion proteins, supporting the protective mucosal layer, and/or directly sequestering chemicals. Lastly, host gene expression is regulated by the microbiome, including CYP450s, multi-drug resistance proteins, and the transcription factors that regulate them. While the microbiome affects the host and pharmacokinetics of the xenobiotic, xenobiotics can also influence the viability and metabolism of the microbiome. Our understanding of the complex interconnectedness between host, microbiome, and metabolism will advance with new modeling systems, technology development and refinement, and mechanistic studies focused on the contribution of human and microbial metabolism. Graphical abstract Xenobiotic metabolism and gut microbiome are tightly interconnected. This review highlights major interactions between the gut microbiome, host and xenobiotic that alter xenobiotic metabolism, with a focus on therapeutic drugs. Notably, a xenobiotic's outcome is altered by the gut microbiome directly metabolizing and/or indirectly perturbing host absorption and xenobiotic metabolism.Image 1 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|