Bioinspired microcapsule reactor (MY-E@SS) delivering anti-inflammatory peptide restores intestinal barrier in murine IBD

Managing inflammatory bowel disease (IBD) remains challenging due to its complex pathogenesis and the limitations of current systemic therapies. While biologics and small molecules offer relief, they often come with high costs, risks of secondary non-response, and systemic side effects. Oral gut-restricted therapies, like engineered probiotics, are emerging as a promising strategy to achieve therapeutic effects directly within the intestinal mucosa, minimizing systemic exposure and addressing the critical need for targeted delivery and improved patient outcomes in IBD.

Researchers developed a core-shell bionic microcapsule reactor, named MY-E@SS, designed to safely deliver engineered bacteria through the gastrointestinal tract. Upon reaching inflamed intestinal sites in a male murine model of inflammatory bowel disease, these bacteria were engineered to sense the pathological microenvironment and responsively release an anti-inflammatory peptide. The study assessed the system's biocompatibility and therapeutic efficacy by evaluating intestinal barrier integrity, systemic inflammation, oxidative stress, respiratory metabolism, and microbial homeostasis.

The MY-E@SS system demonstrated excellent biocompatibility and pronounced therapeutic efficacy in the murine IBD model. It successfully restored intestinal barrier integrity, which is crucial for preventing pathogen translocation and maintaining gut health. Furthermore, the system significantly attenuated systemic inflammation and oxidative stress, key drivers of IBD pathology. The engineered probiotics also modulated respiratory metabolism and reestablished microbial homeostasis within the gut. Mechanistically, these therapeutic effects were attributed to the inhibition of the TNF-α/NF-κB signaling pathway, a central regulator of inflammation.

The MY-E@SS system demonstrated pronounced therapeutic efficacy, restoring intestinal barrier integrity and significantly attenuating systemic inflammation and oxidative stress in the murine IBD model.