Work

A probiotic–drug cascade system for inflammatory bowel disease via tryptophan metabolism and gut microbiome remodeling

Year: 2026

Type: article

Abstract: The development of oral therapeutics capable of improving tryptophan metabolism and restoring gut microbiome homeostasis is vital for effective inflammatory bowel disease (IBD) management. Despite the significant advancements in bacteriotherapy for IBD, current strategies often suffer from limited functionalities and compromised efficacy due to the multifaceted nature of gastrointestinal tract physiology and pathology. Here, we propose an acid-resistant and microenvironment-responsive probiotic-drug codelivery system (BS@MPN-BBR@S100) based on the metal-phenolic network (MPN). Following oral administration, the dual MPN-S100 coating significantly enhances probiotic survival in the face of gastrointestinal challenges, including gastric acid and proteases, promoting targeted adhesion to colonic lesions. Impressively, the loaded berberine (BBR) is released in a targeted, calprotectin (CP)-responsive manner at disease sites, thereby effectively restoring intestinal barrier function by remodeling tryptophan metabolism. In a murine model of colitis, BS@MPN-BBR@S100 effectively alleviated disease symptoms by regulating tryptophan metabolism, reshaping microbiome homeostasis, and alleviating oxidative stress. Overall, this study addresses key bottlenecks in oral probiotics and drug delivery, offering a promising strategy for developing effective therapeutics against IBD.

Source: Acta Pharmaceutica Sinica B

DOI: 10.1016/j.apsb.2026.07.013