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Commensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectors

GSE315035 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/30 Platform GPL24247
Summary
In vivo delivery systems (IDS) are designed to protect and transport therapeutics, but their efficacy is limited by low delivery efficiency. Here, we reveal that intestinal microbiota critically modulates IDS delivery efficiency by promoting hepatic clearance, whereas disrupting host-microbe interactions markedly enhances drug and gene delivery. Mechanistically, intestinal epithelial sensing of microbial stimuli triggers serotonin production that activates Kupffer cells. Transient inhibition of serotonin signaling, via receptor blockade or dietary intervention, attenuates hepatic clearance and improves systemic delivery. This strategy enhances the efficacy of IDS-based chemotherapy and oncolytic virotherapy and enables body-wide improvements in somatic genome editing and mRNA-based protein replacement. Together, these findings uncover a gut-liver immune axis that broadly constrains IDS performance, offering general approaches to improving in vivo therapeutic delivery.
Published in
Commensal-driven serotonin production modulates in vivo delivery of synthetic and viral vectors
Wang Q, Chen Z, Zhang G et al. · Science (New York, N.Y.) 2026 · PMID 41855345 · doi:10.1126/science.adu7686
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Also filed as BioProject PRJNA1166851 and SRA study SRP657792. Searching any of these in the dataset finder brings you back here.

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