Stress-trained microalgae robots with probiotics backpack and intestinal brake for inflammatory bowel disease management.

Stress training of Haematococcus pluvialis resulted in a thickened cell wall that conferred gastric resilience while maintaining flagella-driven motility.

• Stress-trained HP developed a thickened cell wall compared to non-trained HP.
• Trained HP maintained flagella-driven motility after stress conditioning.
• The thickened cell wall enabled the microalgae to survive the harsh gastric environment.
• Stress training also enhanced astaxanthin (AST) production in HP.

Polydopamine (PDA) coating of Escherichia coli Nissle 1917 (EcN) enabled anchoring onto HP via host-guest interactions and preserved EcN viability.

• PDA-coated EcN was anchored onto HP through host-guest interactions.
• In vivo, PDA preserved EcN activity during gastric transit.
• PDA coating enabled specific adhesion of EcN to inflamed intestinal sites.
• The combination formed the EcN@PDA@HP biohybrid robot.

The EcN@PDA@HP biohybrid robot enabled rapid gastric passage and precise retention in inflamed intestinal regions.

• The system was designed to address the challenge that current delivery systems cannot adequately protect active agents through the harsh gastric environment.
• The intestinal braking system component enabled precise retention at inflamed sites.
• Flagella-driven motility of stress-trained HP contributed to active navigation.
• The system combined an intestinal braking mechanism with active motility for targeted delivery.

EcN@PDA@HP effectively alleviated IBD in male murine models by combining ROS scavenging and microbiota restoration.

• In vivo experiments were conducted in male murine IBD models.
• The therapeutic effect involved ROS scavenging attributed to astaxanthin from HP.
• Microbiota restoration was attributed to bacteriotherapy via EcN probiotic activity.
• The combination of antioxidizing AST and bacteriotherapy produced effective IBD alleviation.
• The system was described as offering a promising strategy for diverse IBD conditions.

Current delivery systems inadequately protect active agents such as antioxidants and probiotics through the gastric environment and fail to precisely deliver them to inflamed intestinal sites.

• IBD involves elevated intestinal reactive oxygen species (ROS) and microbial imbalance.
• The inability to protect antioxidants and probiotics through the gastric environment was identified as a key challenge.
• Lack of precise delivery to inflamed intestinal sites was identified as a major limitation of existing systems.
• These limitations motivated the development of the EcN@PDA@HP biohybrid robot.