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.

中文翻译：

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连接点：针对药物毒性中的微生物组

肠道微生物群对人类健康有着巨大的影响，它在引发、加重或改善疾病方面的作用开始显现。最近，它对异质毒理学反应的贡献也受到关注，特别是在药物诱导的毒性方面。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，从而导致毒性改变。目前的研究更多地关注异生素如何干扰肠道微生物组成和功能的单向影响，从而导致体内平衡的改变。然而，肠道菌群与异生素之间的相互作用是双向的，肠道菌群对异生素，尤其是药物的影响不容忽视。因此，在本次审查中，我们专注于肠道微生物群如何通过突出微生物组、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之间的点联系起来，以促进与药物毒性相关的微生物靶标和机制的发现。除此之外，总结和讨论了当前通过靶向微生物组来控制药物毒性的主流策略。该综述为创新药研发中的药性评价以及未来探索通过靶向微生物组降低药物毒性的策略提供了技术参考。微生物酶或代谢物、药物代谢物和宿主毒理学反应，以促进发现与药物毒性相关的微生物靶标和机制。除此之外，总结和讨论了当前通过靶向微生物组来控制药物毒性的主流策略。该综述为创新药研发中的药性评价以及未来探索通过靶向微生物组降低药物毒性的策略提供了技术参考。微生物酶或代谢物、药物代谢物和宿主毒理学反应，以促进发现与药物毒性相关的微生物靶标和机制。除此之外，总结和讨论了当前通过靶向微生物组来控制药物毒性的主流策略。该综述为创新药研发中的药性评价以及未来探索通过靶向微生物组降低药物毒性的策略提供了技术参考。