肠道菌群驱动的血清素产生调节合成和病毒载体的体内递送

Commensal- driven serotonin production modulates in vivo delivery of synthetic and viral vectors Qin Wang1†, Ziqi Chen1†, Guorong Zhang1†, Jiale Yang1, Runfan Hu1, Tongyue Yao1, Cici Zeng1,2, Shugeng Zhang3, Wei Jiang1,4,5*, Shu Zhu1,2*, Yucai Wang1,2,4,5* 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. …