Decorating probiotics with a triggerable and catalytic shell for synergistically enhanced colitis biotherapy

Abstract

Probiotics have creditableness in adjunctive therapy for ulcerative colitis, but their physiological activity and alleviation efficiency are frequently compromised by gastrointestinal conditions and oxidative stress microenvironments. Here, we developed a probiotic-based therapeutic that synergistically ameliorates colonic structure, intestinal redox, and microbiota homeostasis. Probiotics were initially coated with a metal-phenolic shell to provide a network for spatially loading antioxidant enzymes, and then wrapped with a pH-triggerable enteric layer to enable on-demand reactivation in the inflamed colon. Upon oral administration, the pH-triggerable enteric layer efficiently enhanced gastric acid resistance and on-demand release of enzyme-loaded probiotics in the inflamed colon, enabling efficient reactive oxygen species scavenging and salutary gut microbiota regulation at the lesional regions. In multiple mouse models, this therapeutic normalized immunologic balance and mitigated colonic damage with high efficacy, thus representing a powerful strategy for colitis therapy.