药物反应（IVDR）的个体差异可能是药物不良反应（ADR）和延长治疗时间的主要原因，从而造成巨大的健康和经济负担。尽管药物基因组学对个体遗传背景对药代动力学 (PK) 和药效学 (PD) 的影响进行了广泛的研究，但遗传多样性只能解释有限比例的 IVDR。最近的研究强调了肠道微生物群（也称为第二基因组）及其代谢物在调节人类疾病治疗结果中的作用。因此，药物微生物组学这一新兴领域旨在探索微生物群变异与 IVDR 或 ADR 之间的相关性。这篇综述对肠道微生物群与人类全身疾病（包括癌症、心血管疾病（CVD）、内分泌疾病等）的经典治疗药物之间复杂的相互作用进行了最新概述。我们总结了微生物群如何直接和间接改变药物的吸收、分布、代谢和排泄 (ADME)。相反，药物还可以调节肠道微生物群的组成和功能，导致微生物代谢和免疫反应的变化。我们还讨论了该领域的实际挑战、策略和机遇，强调迫切需要开发多组学创新方法，整合各种数据类型，包括人类和微生物组基因组数据，以及将实验室数据转化为临床实践。总而言之，药物微生物组学是解决 IVDR 和改善患者治疗效果的一个有前途的途径，必须在该领域开展进一步研究，以充分发挥其精准医疗的潜力。© 2023。四川大学华西医院。

Individual variability in drug response (IVDR) can be a major cause of adverse drug reactions (ADRs) and prolonged therapy, resulting in a substantial health and economic burden. Despite extensive research in pharmacogenomics regarding the impact of individual genetic background on pharmacokinetics (PK) and pharmacodynamics (PD), genetic diversity explains only a limited proportion of IVDR. The role of gut microbiota, also known as the second genome, and its metabolites in modulating therapeutic outcomes in human diseases have been highlighted by recent studies. Consequently, the burgeoning field of pharmacomicrobiomics aims to explore the correlation between microbiota variation and IVDR or ADRs. This review presents an up-to-date overview of the intricate interactions between gut microbiota and classical therapeutic agents for human systemic diseases, including cancer, cardiovascular diseases (CVDs), endocrine diseases, and others. We summarise how microbiota, directly and indirectly, modify the absorption, distribution, metabolism, and excretion (ADME) of drugs. Conversely, drugs can also modulate the composition and function of gut microbiota, leading to changes in microbial metabolism and immune response. We also discuss the practical challenges, strategies, and opportunities in this field, emphasizing the critical need to develop an innovative approach to multi-omics, integrate various data types, including human and microbiota genomic data, as well as translate lab data into clinical practice. To sum up, pharmacomicrobiomics represents a promising avenue to address IVDR and improve patient outcomes, and further research in this field is imperative to unlock its full potential for precision medicine.© 2023. West China Hospital, Sichuan University.