Wang Jinyi, Zhou Tingting
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. 2025 Jan;45(1):311-343. doi: 10.1002/med.22077. Epub 2024 Aug 24.
Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.
药物安全是药物研发领域的首要关注点，在此背景下，研究人员越来越关注肠道微生物群的双向调节作用。肠道微生物群在维持药物安全方面起着至关重要的作用。它可以通过多种机制影响药物在体内的转运过程，从而调节其疗效和毒性。主要机制包括：（1）肠道微生物群直接与药物相互作用，改变其化学结构以降低毒性并增强疗效，从而影响药物转运机制，药物也可以改变肠道细菌的结构和丰度；（2）肠道微生物群对肠道屏障通透性的双向调节，促进无毒药物的吸收并抑制有毒成分的吸收；（3）肠道微生物群对转运蛋白表达和活性的双向调节，选择性地促进有效成分的吸收或抑制有毒成分的吸收。这种双向调节作用使肠道微生物群在维持体内药物平衡和减少不良反应方面发挥关键作用。了解这些调节机制有助于揭示减少毒副作用、增强药物疗效并最终提高药物安全性的新方法。本综述从上述方面系统地研究了肠道微生物群在药物转运中的双向调节作用，强调了它们在确保药物安全方面的重要性。此外，它从提高治疗效果和降低药物毒性的角度提供了前瞻性展望，强调了在这一研究领域进一步探索的重要性。其目的是为药物研发和治疗提供更有效的策略。
