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毒理微生物组学:人类微生物组与药物、饮食及环境中的外源性化学物质

Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics.

作者信息

Abdelsalam Nehal Adel, Ramadan Ahmed Tarek, ElRakaiby Marwa Tarek, Aziz Ramy Karam

机构信息

The Center for Genome and Microbiome Research, Cairo University, Cairo, Egypt.

Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

出版信息

Front Pharmacol. 2020 Apr 16;11:390. doi: 10.3389/fphar.2020.00390. eCollection 2020.

Abstract

The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.

摘要

异源生物对环境和人类健康的有害影响正得到更广泛的认识;然而,人类个体间和个体内的基因变异会调节危害程度,主要是通过调节异源生物代谢和解毒的结果来实现。由于人类基因组计划表明,宿主的基因、表观遗传和调控变异不足以解释异源生物代谢中个体间变异性的复杂性,因此其后续的人类微生物组计划正在研究这种变异性如何受到与人类相关的微生物群落的影响。异源生物与微生物组的关系是相互且动态的。人类微生物组不仅对异源生物具有直接的代谢潜力,还能影响宿主代谢基因的表达和宿主酶的活性。另一方面,异源生物可能会改变微生物组的组成,导致生态失调状态,这与多种疾病和不良健康结果有关,包括一些异源生物的毒性增加。毒理微生物组学研究不断变化的微生物组云与各种来源的异源生物之间的这些相互影响,重点关注它们的归宿和毒性,以及各类微生物异源生物修饰酶。这篇综述文章讨论了毒理微生物组学的经典和最新发现,并举例说明了肠道、皮肤、泌尿生殖系统和口腔微生物组与药物、食物来源和环境异源生物之间的相互作用。文章还讨论了毒理微生物组学研究的现状和未来前景,并对进行此类研究的工具和策略进行了全面且批判性的比较。

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