“Tailor-made” polyphenol–prebiotic nanoarmor for pathology-responsive probiotic therapy of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic relapsing disorder driven by disruption of the intestinal microenvironment and gut microbiota homeostasis, accompanied by excessive reactive oxygen species (ROS) production, barrier damage, and immune dysregulation. Conventional oral therapies suffer from several limitations, including poor stability in the harsh gastrointestinal environment, susceptibility to oxidative stress, and insufficient colonization at sites of inflammation. Therapeutic strategies that employ probiotic delivery based on natural products hold great promise for overcoming current limitations in probiotic administration by enabling precise targeting, stimulus-responsive coating disassembly, and improved therapeutic efficacy. Here, we report an inflammation-responsive, nanoengineered probiotic (EcN@QR-Fe/OA-Xylan). Exploiting the microbiota-selective degradation of xylan in the lower intestine, natural-product oleanolic acid and xylan were co-assembled into OA-Xylan nanoparticles as an outer prebiotic “armor” that endows probiotics with intestinal “navigation”. EcN was sequentially coated with a quercetin/Fe³⁺ metal–phenolic network and OA-Xylan to form EcN@QR-Fe/OA-Xylan, which improves gastric survival and oxidative-stress resistance and undergoes transferrin-triggered de-coating for inflammation-site “on-demand awakening”. Collectively, the engineered probiotics achieve synergistic IBD intervention through probiotic protection and lesion-responsive activation, ROS scavenging, and coordinated immune and barrier regulation, offering a “tailor-made” microecology–nanomedicine platform for future IBD therapy.