肠道菌介导的药物毒性及机制研究进展

Research progress of drug toxicity mechanism based on the gut microbiota

药物毒性及机制研究是药物在临床安全使用的重要内容,备受关注。肠道菌群对药物的代谢转化、药效及作用机制具有重大意义,可作为代谢器官在物质信息传递、生物转化等方面发挥重要作用。然而,越来越多的研究发现,肠道菌与某些药物毒性密切相关。一方面,药物会在肠道菌的作用下转化成毒性代谢产物诱发药物的直接毒性;另一方面,肠道菌群会在药物的作用下改变组成和功能,导致内源性代谢通路的紊乱,进而使肠屏障受损而影响其他器官产生药物的间接毒性。本文总结了近年来由肠道菌引发的药物毒性的相关实例,探讨了肠道菌特征代谢酶可能是口服药物毒性产生的重要原因,并对未来肠道菌与药物毒性及机制研究进行了展望,为药物在临床的合理使用及新药的安全性评价提供了新见解。

The exploration of drug toxicity and mechanisms is a vital component in ensuring the safe use of drugs in clinical practice,as this topic has attracted widespread concern.The intestinal flora holds great significance for drug metabolism,efficacy and mechanism,and is an instrumental metabolic organ that facilitates material information transfer and biotransformation.However,an increasing number of studies have shown that intestinal bacteria are closely related to the toxicity of specific drugs.On the one hand,drugs are transformed into toxic metabolites under the influence of intestinal bacteria,thus inducing direct drug toxicity.On the other hand,the composition and function of the intestinal flora are altered under drug influence,resulting in disruption of endogenous metabolic pathways.Consequently,this disruption compromises the intestinal barrier and affects other organs,leading to indirect drug toxicity.This review meticulously compiles recent examples of drug toxicity attributed to intestinal bacteria,explores in depth the contention that metabolic enzymes of gut microbiota may be of great influence on oral drug toxicity,and outlines prospective avenues for future research on gut microbiota and drug toxicity and mechanisms.This not only provides novel perspectives for the judicious clinical utilization of drugs but also offers insights for the safety assessment of innovative pharmaceuticals.