Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Expert Opin Drug Metab Toxicol. 2024 Jul;20(7):593-606. doi: 10.1080/17425255.2024.2365254. Epub 2024 Jun 24.
There is a growing need for alternative models to advance current non-clinical experimental models because they often fail to accurately predict drug responses in human clinical trials. Human organ-on-a-chip models have emerged as promising approaches for advancing the predictability of drug behaviors and responses.
We summarize up-to-date human gut-on-a-chip models designed to demonstrate intricate interactions involving the host, microbiome, and pharmaceutical compounds since these models have been reported a decade ago. This overview covers recent advances in gut-on-a-chip models as a bridge technology between non-clinical and clinical assessments of drug toxicity and metabolism. We highlight the promising potential of gut-on-a-chip platforms, offering a reliable and valid framework for investigating reciprocal crosstalk between the host, gut microbiome, and drug compounds.
Gut-on-a-chip platforms can attract multiple end users as predictive, human-relevant, and non-clinical model. Notably, gut-on-a-chip platforms provide a unique opportunity to recreate a human intestinal microenvironment, including dynamic bowel movement, luminal flow, oxygen gradient, host-microbiome interactions, and disease-specific manipulations restricted in animal and cell culture models. Additionally, given the profound impact of the gut microbiome on pharmacological bioprocess, it is critical to leverage breakthroughs of gut-on-a-chip technology to address knowledge gaps and drive innovations in predictive drug toxicology and metabolism.
由于当前非临床实验模型往往无法准确预测药物在人体临床试验中的反应,因此人们越来越需要替代模型来推进研究。人体器官芯片模型作为一种有前途的方法,已经出现,用于提高药物行为和反应的可预测性。
自十年前报道以来,我们总结了最新的人肠道芯片模型,这些模型旨在展示涉及宿主、微生物组和药物化合物的复杂相互作用。本综述涵盖了肠道芯片模型作为非临床和临床评估药物毒性和代谢的桥梁技术的最新进展。我们强调了肠道芯片平台的有前途的潜力,为研究宿主、肠道微生物组和药物化合物之间的相互交流提供了可靠和有效的框架。
肠道芯片平台可以吸引多个终端用户,作为预测性、与人类相关和非临床模型。值得注意的是,肠道芯片平台为重现人类肠道微环境提供了独特的机会,包括动态肠蠕动、腔道流动、氧气梯度、宿主-微生物组相互作用以及动物和细胞培养模型中受到限制的疾病特异性操作。此外,鉴于肠道微生物组对药物生物过程的深远影响,利用肠道芯片技术的突破来解决知识空白并推动预测性药物毒理学和代谢方面的创新至关重要。