A Microbial Community Cultured in Gradient Hydrogel for Investigating Gut Microbiome‐Drug Interaction and Guiding Therapeutic Decisions

材料科学 药品 肠道微生物群 微生物群 计算生物学 生物 纳米技术 药理学 生化工程 生物信息学 工程类
作者
Di‐Wei Zheng,Ji‐Yan Qiao,Jun‐Chi Ma,Jiaxin An,Chi‐Hui Yang,Yu Zhang,Qian Cheng,Zhi‐Yong Rao,Simin Zeng,Li Wang,Xian‐Zheng Zhang
出处
期刊:Advanced Materials [Wiley]
卷期号:35 (22) 被引量:12
标识
DOI:10.1002/adma.202300977
摘要

Despite the recognition that the gut microbiota acts a clinically significant role in cancer chemotherapy, both mechanistic understanding and translational research are still limited. Maximizing drug efficacy requires an in-depth understanding of how the microbiota contributes to therapeutic responses, while microbiota modulation is hindered by the complexity of the human body. To address this issue, a 3D experimental model named engineered microbiota (EM) is reported for bridging microbiota-drug interaction research and therapeutic decision-making. EM can be manipulated in vitro and faithfully recapitulate the human gut microbiota at the genus/species level while allowing co-culture with cells, organoids, and isolated tissues for testing drug responses. Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism. Guided by discovered mechanisms, custom-tailored strategies are adopted to maximize the therapeutic efficacy of drugs on orthotopic tumor models with patient-derived gut microbiota. These strategies include immune synergy, nanoparticle encapsulation, and host-guest complex formation, respectively. Given the important role of the gut microbiota in influencing drug efficacy, EM will likely become an indispensable tool to guide drug translation and clinical decision-making.
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