Title : Natural nanoarmored probiotic with inflammation-responsive activation for precision oral intervention of colitis
Abstract:
Oral probiotic therapy has emerged as a promising strategy for the management of Inflammatory Bowel Disease (IBD), yet its therapeutic efficacy remains severely restricted by three major barriers: poor survival during gastrointestinal transit, insufficient retention at inflamed intestinal sites, and limited ability to remodel the oxidative and inflammatory microenvironment. In this work, we developed a natural nanoarmored probiotic system with inflammation-responsive activation to achieve precise oral intervention of colitis.
Escherichia coli Nissle 1917 (EcN) was sequentially coated with a quercetin-Fe³⁺ metal-phenolic network and an outer oleanolic acid/xylan layer to construct a bilayer protective shell. This design integrates the biological safety of food-related natural components with the functional advantages of nanotechnology. The outer xylan-containing layer improves gastrointestinal stability and provides intestine-oriented delivery through microbial degradability in the lower gut, while the quercetin-Fe³⁺ network enhances resistance against acidic, oxidative, and enzymatic stress during oral administration. More importantly, the nanoarmor remains protective during transit but undergoes pathological microenvironment-triggered disassembly at inflamed intestinal sites, thereby restoring bacterial activity at the desired location and time.
The engineered probiotic exhibited improved viability under simulated gastrointestinal conditions, enhanced mucosal interaction, and superior colon retention in colitis models. After activation at the lesion site, the system effectively reduced reactive oxygen species, alleviated inflammatory damage, and promoted the recovery of intestinal homeostasis. In addition, the xylan-based outer layer may exert prebiotic effects that further support gut microbiota regulation, contributing to synergistic therapeutic benefit.
This study presents a food-derived, naturally engineered probiotic platform featuring transport protection, lesion-responsive awakening, and local microenvironment regulation. The proposed strategy offers a promising route toward safer and more effective probiotic-based interventions for intestinal inflammation, while also broadening the application of food nanotechnology in precision health and functional biotherapeutics.
