研究组确定肠道微生物群是基于IDS的治疗效果的关键调节因子，并且破坏共生宿主相互作用显着改善药物和基因传递。肠上皮细胞感知微生物刺激并通过血清素的产生远程激活Kupffer细胞，从而驱动肝脏IDS清除。短暂抑制5-羟色胺信号，通过受体阻断或饮食干预，减轻肝IDS清除和提高输送效率。该策略在化疗和溶瘤病毒治疗方面产生了三倍以上的治疗效果，在体细胞基因组编辑和基于信使RNA的治疗方面产生了5至15倍的效果。这些发现揭示了一种肠道-肝脏免疫轴，可以用于改善基于IDS的癌症和基因治疗。
研究人员表示，体内给药系统（IDSs）旨在保护和运输治疗药物，但其临床应用受到低递送效率的阻碍。
附：英文原文
Title: Commensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectors
Author: Qin Wang, Ziqi Chen, Guorong Zhang, Jiale Yang, Runfan Hu, Tongyue Yao, Cici Zeng, Shugeng Zhang, Wei Jiang, Shu Zhu, Yucai Wang
Issue&Volume: 2026-03-19
Abstract: In vivo delivery systems (IDSs) are designed to protect and transport therapeutics, but their clinical applications are hindered by low delivery efficiency. We identified gut microbiota as key regulators of efficacy of IDS-based therapies and that disrupting commensal-host interactions markedly improves drug and gene delivery. Intestinal epithelial cells sense microbial stimulation and remotely activate Kupffer cells through serotonin production, thereby driving hepatic IDS clearance. Transient suppression of serotonin signaling, through receptor blockade or dietary intervention, mitigates hepatic IDS clearance and improves delivery efficiency. This strategy yielded more than threefold therapeutic enhancement in chemotherapy and oncolytic virotherapy and 5- to 15-fold improvements in somatic genome editing and messenger RNA–based therapies. These findings reveal a gut-liver immune axis that can be therapeutically exploited to improve IDS-based cancer and gene therapies.
DOI: adu7686
Source: https://www.science.org/doi/10.1126/science.adu7686