Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, China.
Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai, China.
Med Res Rev. 2022 Jan;42(1):83-111. doi: 10.1002/med.21805. Epub 2021 Apr 15.
The gut microbiota has a vast influence on human health and its role in initiating, aggravating, or ameliorating diseases is beginning to emerge. Recently, its contribution to heterogeneous toxicological responses is also gaining attention, especially in drug-induced toxicity. Whether they are orally administered or not, drugs may interact with the gut microbiota directly or indirectly, which leads to altered toxicity. Present studies focus more on the unidirectional influence of how xenobiotics disturb intestinal microbial composition and functions, and thus induce altered homeostasis. However, interactions between the gut microbiota and xenobiotics are bidirectional and the impact of the gut microbiota on xenobiotics, especially on drugs, should not be neglected. Thus, in this review, we focus on how the gut microbiota modulates drug toxicity by highlighting the microbiome, microbial enzyme, and microbial metabolites. We connect the dots between drugs, the microbiome, microbial enzymes or metabolites, drug metabolites, and host toxicological responses to facilitate the discovery of microbial targets and mechanisms associated with drug toxicity. Besides this, current mainstream strategies to manipulate drug toxicity by targeting the microbiome are summarized and discussed. The review provides technical reference for the evaluation of medicinal properties in the research and development of innovative drugs, and for the future exploitation of strategies to reduce drug toxicity by targeting the microbiome.
肠道微生物群对人类健康有巨大影响，其在引发、加重或改善疾病方面的作用开始显现。最近，其在异源性毒理学反应中的作用也引起了关注，特别是在药物诱导的毒性中。无论是否口服，药物都可能直接或间接与肠道微生物群相互作用，导致毒性改变。目前的研究更侧重于外来物质如何扰乱肠道微生物组成和功能，从而导致内稳态改变的单向影响。然而，肠道微生物群和外来物质之间的相互作用是双向的，不能忽视肠道微生物群对外来物质，特别是药物的影响。因此，在这篇综述中，我们重点讨论了肠道微生物群如何通过强调微生物组、微生物酶和微生物代谢物来调节药物毒性。我们将药物、微生物组、微生物酶或代谢物、药物代谢物和宿主毒理学反应联系起来，以促进与药物毒性相关的微生物靶点和机制的发现。除此之外，还总结和讨论了目前通过靶向微生物群来操纵药物毒性的主流策略。该综述为评价药物特性、研发创新药物以及未来通过靶向微生物群来降低药物毒性的策略提供了技术参考。
