Integrating metabolomics, bionics, and culturomics to study probiotics-driven drug metabolism.
Integrating metabolomics, bionics, and culturomics to study probiotics-driven drug metabolism.
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DOI：
10.3389/fphar.2023.1047863
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发表时间：
2023
影响因子：
5.6
通讯作者：
Chen, Yongfu
中科院分区：
文献类型：
--
作者：
Li, Bohai;Kwok, Lai-Yu;Wang, Dandan;Li, Lu;Guo, Shuai;Chen, Yongfu
许多药物已被证明是由人体肠道微生物代谢的，但益生菌驱动的药物代谢能力很少被探索。在这里，我们开发了一个综合代谢组学、培养组学和仿生学框架来系统地研究益生菌驱动的药物代谢。我们发现75%（27/36）的被测药物被5种选定的益生菌代谢，含有硝基或偶氮基团的药物更容易被代谢。作为原理验证实验，我们发现干酪乳杆菌（Lacticaseibacillus casei Zhang， LCZ）可以在单培养、接近真实的模拟人体消化系统和离体粪便共培养系统中代谢消旋卡多曲为活性产物s -乙酰硫孤儿和硫孤儿。然而，在干酪乳杆菌张的消旋卡多曲代谢活性中观察到个性化效应，这取决于个体的宿主肠道微生物组组成。基于我们的工作流程生成的数据，我们提出了干酪乳杆菌、消旋卡多曲和宿主肠道微生物群之间可能的相互作用机制，为益生菌-药物联合治疗提供了实践指导，并为精准益生菌提供了新的见解。
Many drugs have been shown to be metabolized by the human gut microbiome, but probiotic-driven drug-metabolizing capacity is rarely explored. Here, we developed an integrated metabolomics, culturomics, and bionics framework for systematically studying probiotics-driven drug metabolism. We discovered that 75% (27/36 of the assayed drugs) were metabolized by five selected probiotics, and drugs containing nitro or azo groups were more readily metabolized. As proof-of-principle experiments, we showed that Lacticaseibacillus casei Zhang (LCZ) could metabolize racecadotril to its active products, S-acetylthiorphan and thiorphan, in monoculture, in a near-real simulated human digestion system, and in an ex vivo fecal co-culture system. However, a personalized effect was observed in the racecadotril-metabolizing activity of L. casei Zhang, depending on the individual’s host gut microbiome composition. Based on data generated by our workflow, we proposed a possible mechanism of interactions among L. casei Zhang, racecadotril, and host gut microbiome, providing practical guidance for probiotic-drug co-treatment and novel insights into precision probiotics.
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