Berberine (BBR), an isoquinoline alkaloid, has been found in many plants, such as Coptis chinensis Franch and Phellodendron chinense Schneid. Although BBR has a wide spectrum of pharmacological effects, its oral bioavailability is extremely low. In recent years, gut microbiota has emerged as a cynosure to understand the mechanisms of action of herbal compounds. Numerous studies have demonstrated that due to its low bioavailability, BBR can interact with the gut microbiota, thereby exhibiting altered pharmacological effects. However, no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects. Here, we describe the direct interactive relationships between BBR and gut microbiota, including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota. In addition, the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed. Furthermore, we provide our viewpoint on future research directions regarding BBR and gut microbiota. This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.

小檗碱 (BBR) 是一种异喹啉生物碱，已在许多植物中发现，如黄连和黄柏施耐德。虽然 BBR 具有广泛的药理作用，但其口服生物利用度极低。近年来，肠道微生物群已成为了解草药化合物作用机制的关键。大量研究表明，由于生物利用度低，BBR 可以与肠道微生物群相互作用，从而表现出改变的药理作用。然而，没有系统和全面的综述总结这些相互作用及其对药理作用的相应影响。在这里，我们描述了 BBR 和肠道微生物群之间的直接交互关系，包括 BBR 对肠道微生物群组成和代谢的调节以及肠道微生物群对 BBR 的代谢。此外，讨论了肠道微生物群和 BBR 之间的复杂相互作用以及 BBR 的副作用和个性化使用。此外，我们就 BBR 和肠道微生物群的未来研究方向提供了我们的观点。本综述不仅有助于解释 BBR 活性的机制，而且为临床实践中合理使用 BBR 提供支持。