APC Microbiome Ireland, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland.
School of Pharmacy, University College Cork, Cork, Ireland.
Pharmacol Res. 2018 Jul;133:170-186. doi: 10.1016/j.phrs.2018.04.009. Epub 2018 Apr 13.
Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research. This review considers a potential mechanism, 'microbial bile acid metabolism', by which the intricate interplay between the host and gut bacteria may influence drug pharmacokinetics. Bile salts traditionally regarded as biological surfactants, synthesized by the host and biotransformed by gut bacteria, are now also recognized as signalling molecules that affect diverse physiological processes. Accumulating data indicate that bile salts are not equivalent with respect to their physicochemical properties, micellar solubilization capacities for poorly water-soluble drugs, crystallization inhibition tendencies nor potencies for bile acid receptor activation. Herein, the origin, physicochemical properties, physiological functions, plasticity and pharmaceutical significance of the human bile acid pool are discussed. Microbial dependant differences in the composition of the human bile acid pool, simulated intestinal media and commonly used preclinical species is highlighted to better understand in vivo performance predictiveness. While the precise impact of an altered gut microbiome, and consequently bile acid pool, in the biopharmaceutical setting remains largely elusive, the objective of this article is to aid knowledge acquisition through a detailed review of the literature.
曾经被认为晦涩难懂且不受重视的肠道微生物群（定植在胃肠道的微生物群落），如今正逐渐被人们认识到是影响人类健康诸多方面的重要因素。个体间这些共生微生物与肠道关联的广泛差异也越发明显，这为探索其对疾病和治疗反应的影响带来了新的研究课题。在这方面，微生物群的药物代谢能力的发掘为微生物学和药理学研究的融合提供了动力。本篇综述探讨了一种潜在的机制，即“微生物胆酸代谢”，通过这种机制，宿主与肠道细菌之间的复杂相互作用可能会影响药物的药代动力学。传统上被认为是生物表面活性剂的胆盐，由宿主合成并经肠道细菌生物转化，现在也被认为是影响多种生理过程的信号分子。越来越多的数据表明，胆盐在其理化性质、对亲脂性差的药物的胶束增溶能力、结晶抑制倾向以及胆汁酸受体激活的效力方面并不等同。本文讨论了人胆汁酸库的来源、理化性质、生理功能、可塑性和药物学意义。强调了人胆汁酸库在组成、模拟肠内介质和常用临床前物种方面的微生物依赖性差异，以更好地理解体内性能的预测性。虽然肠道微生物组（以及随之而来的胆汁酸库）在生物制药环境中的改变的确切影响在很大程度上仍难以捉摸，但本文的目的是通过详细的文献回顾来帮助获取知识。
