A “Janus” structured nanoclay microgel system for targeted probiotic therapy in diarrhea-predominant irritable bowel syndrome

Probiotic therapy holds potential for preventing and treating various gastrointestinal diseases, including diarrhea-predominant irritable bowel syndrome (IBS-D). Previous studies have suggested that it can help restore intestinal mucosal immunity and gut microbiota dysbiosis in IBS-D patients. Probiotics regulate host microbial metabolism and immune homeostasis, thereby improving host health. Effective and persistent colonization is crucial for probiotic therapy, but oral probiotics often suffer from limited efficacy due to loss of biological activity and insufficient colonization in the complex intestinal environment. Currently, formulations that specifically target gut mucosal colonization are scarce. We developed a "Janus" structured nanoclay microgel via microfluidics encapsulating Pediococcus pentosaceus Li05 (Li05) towards this end. Polydopamine enhanced the microgel's adhesion to the intestinal mucosa, prolonging its residence time in the intestine and enabling targeted delivery of active Li05. The nanoclay promoted Li05 aggregation and growth through charge adsorption, preserving its biological activity and ensuring an effective dose for gut colonization. In vivo studies demonstrated that the nanoclay microgel significantly alleviated diarrhea, mucosal inflammation, and gut microbiota dysbiosis in an IBS-D rat model. These findings suggest that this nanoclay microgel is an effective gut targeted formulation able to promote probiotic growth, offering new approaches for future probiotic therapy in IBS-D.