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The gut microbiome: an orchestrator of xenobiotic metabolism.
Acta Pharmaceutica Sinica B ( IF 14.5 ) Pub Date : 2019-12-10 , DOI: 10.1016/j.apsb.2019.12.001
Stephanie L Collins 1 , Andrew D Patterson 2
Affiliation  

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.

中文翻译:

肠道微生物组:异种生物代谢的协调者。

居住在人类肠道中的微生物代表了异源生物的新陈代谢位点。肠道微生物组是胃肠道中微生物的集合,可以改变药物,环境毒物和重金属的代谢结果,从而改变其药代动力学。肠道微生物组对异生物素的直接化学修饰,无论是通过肠道还是通过肠肝循环重新进入肠道,都可以导致新陈代谢或生物激活的增加,具体取决于微生物生态位内的酶活性。微生物组内编码的独特酶包括逆转宿主解毒途径赋予的修饰的那些酶。此外,微生物组可通过增加细胞-细胞粘附蛋白的表达,支持保护性粘膜层和/或直接隔离化学物质来限制小肠中异源生物的吸收。最后,宿主基因的表达受微生物组的调控,包括CYP450,多药抗性蛋白和调控它们的转录因子。虽然微生物组会影响异源生物的宿主和药代动力学,但异源生物也会影响微生物组的生存能力和代谢。我们将通过新的建模系统,技术开发和完善以及专注于人类和微生物代谢贡献的机理研究,进一步了解宿主,微生物组和代谢之间复杂的相互联系。和/或直接隔离化学品。最后,宿主基因的表达受微生物组的调节,包括CYP450,多药抗性蛋白和调节它们的转录因子。虽然微生物组会影响异源生物的宿主和药代动力学,但异源生物也会影响微生物组的生存能力和代谢。我们将通过新的建模系统,技术开发和完善以及专注于人类和微生物代谢贡献的机理研究,进一步了解宿主,微生物组和代谢之间复杂的相互联系。和/或直接隔离化学品。最后,宿主基因的表达受微生物组的调控,包括CYP450,多药抗性蛋白和调控它们的转录因子。虽然微生物组会影响异源生物的宿主和药代动力学,但异源生物也会影响微生物组的生存能力和代谢。我们将通过新的建模系统,技术开发和完善以及专注于人类和微生物代谢贡献的机理研究,进一步了解宿主,微生物组和代谢之间复杂的相互联系。虽然微生物组会影响异源生物的宿主和药代动力学,但异源生物也会影响微生物组的生存能力和代谢。我们将通过新的建模系统,技术开发和完善以及专注于人类和微生物代谢贡献的机理研究,进一步了解宿主,微生物组和代谢之间复杂的相互联系。虽然微生物组会影响异源生物的宿主和药代动力学,但异源生物也会影响微生物组的生存能力和代谢。我们将通过新的建模系统,技术开发和完善以及专注于人类和微生物代谢贡献的机理研究,进一步了解宿主,微生物组和代谢之间复杂的相互联系。
更新日期:2019-12-11
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