{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310338/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310338"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Transcriptomic analysis of macrophages","description":"The clinical efficacy of cytotoxic nanomedicines is often limited by rapid hepatic clearance, yet the endogenous biological regulators of this process remain incompletely understood. Here, we identify the gut microbiota as a central determinant of nanomedicine biodistribution, acting through transcriptional programming of liver-resident macrophages rather than modulation of adaptive immunity. Using germ-free mice, fecal microbiota transplantation, and targeted microbial perturbation, we show that the nitroimidazole antibiotic metronidazole reconfigures gut microbial ecology and reprograms Kupffer cells into a reduced-uptake state. This shift suppresses hepatic sequestration and enhances tumour accumulation of clinically deployed nanomedicines across multiple cancer models and nanoparticle formulations. Single-cell RNA sequencing reveals a coordinated downregulation of phagocytic and scavenger receptor pathways in Kupffer cells, while metabolomic profiling identifies microbiota-dependent changes in bile acid availability. Restoration of this altered microbial state through fecal transfer is sufficient to transmit the low-clearance phenotype, demonstrating causal and transferable host control of nanomedicine fate. Together, these findings position the gut-liver axis as a tuneable checkpoint for cytotoxic drug pharmacokinetics and introduce microbiome-directed interventions as a distinct strategy to improve nanomedicine delivery.","dates":{"publication":"2026/06/16"},"accession":"GSE310338","cross_references":{"GSM":["GSM9294178","GSM9294179"],"GPL":["24247"],"GSE":["310338"],"taxon":["Mus musculus"]}}