Abstract
Inflammatory bowel disease (IBD) involves elevated intestinal reactive oxygen species (ROS) and microbial imbalance. A key challenge is that current delivery systems cannot adequately protect active agents, such as antioxidants and probiotics, through the harsh gastric environment nor precisely deliver them to inflamed intestinal sites. Here, we present the EcN@PDA@HP biohybrid robot, composed of stress-trained microalgae, probiotics, and an intestinal braking system, enabling rapid gastric passage and precise retention in inflamed regions. Stress-trained Haematococcus pluvialis (HP) developed a thickened cell wall for gastric resilience, maintained flagella-driven motility, and enhanced astaxanthin (AST) production. Polydopamine (PDA)-coated Escherichia coli Nissle 1917 (EcN) anchors onto HP via host-guest interactions. In vivo, PDA preserves EcN activity and enables specific adhesion to inflamed sites. By combining antioxidizing AST and bacteriotherapy, EcN@PDA@HP effectively alleviates male murine IBD models via ROS scavenging and microbiota restoration, offering a promising strategy for diverse IBD conditions.