Chronic kidney disease (CKD) progression is driven in part by persistent microinflammation, with interleukin-1β (IL-1β) playing a key role. To create a targeted anti-inflammatory therapy with reduced systemic toxicity, the authors engineered outer membrane vesicles (OMVs) derived from Bacteroides fragilis to encapsulate a single-chain antibody fragment (scFv) against IL-1β and appended a kidney-targeting peptide (KKEEE)₃K. These engineered OMVs (OMV-(KKEEE)₃K-scFv) demonstrated high stability and precise delivery of the scFv to proximal renal tubule cells in vitro and in vivo, showing excellent safety profiles. In multiple preclinical models — including diabetic nephropathy, lupus nephritis, and unilateral ureteral obstruction — treatment reduced expression of pro-inflammatory cytokines (such as TNF-α, IL-6, MCP-1), decreased inflammatory cell infiltration, and alleviated renal injury and fibrosis.
This article demonstrates a microbiome-derived vesicle-based nanotherapy that effectively delivers biologic anti-inflammatory agents directly to diseased kidney tissue, offering a potentially safer and targeted alternative to conventional systemic antibody therapy for chronic kidney inflammation and related pathologies.
