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

Abstract

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. A schematic diagram of nanoclay microgels targeted for intestinal mucosal colonization, carrying Pediococcus pentosaceus Li05 (Li05), illustrates their adhesion in the intestine, release, and therapeutic effect on diarrhea-predominant irritable bowel syndrome (IBS-D). The “Janus”-structured nanoclay microgel, loaded with Li05, was prepared via microfluidics. These microgels exhibit significant tolerance to gastric fluids, greatly enhancing the viability and bioavailability of Li05. Through polydopamine-mediated adhesion, the microgels closely adhere to the intestine mucosa, prolonging intestinal retention and facilitating probiotics colonization. Subsequent release of nanoclay and Li05 into the target intestinal lumen effectively alleviates mucosal inflammation and microbiota dysbiosis in IBS-D, demonstrating pronounced therapeutic efficacy in a rat model. • A “Janus” structured nanoclay microgel probiotics delivery system is generated by microfluid to promote bioactivity and bioavailability. • Polydopamine on one side of microgel enhances colonic targeting through molecular interactions with the colonic mucosa. • Nanoclay enhances probiotic aggregation and growth on the microgel surface via charge-dependent effects. • Oral microgels show great therapeutic efficacy in IBS-D models, reducing intestinal inflammation and microbiota dysbiosis.