An orally budesonide-loaded yeast microcapsules-based gel relieves IgA nephropathy via the modulation of gut-kidney axis

Abstract

IgA nephropathy (IgAN) is an autoimmune disease marked by IgA complex deposition in the glomerular mesangium, leading to chronic kidney disease and renal failure. Our clinical studies highlighted the critical role of gut microbiota and mucosal immunity in IgAN pathogenesis, identified through 16S rRNA gut microbiota diversity analysis. Given the established gut-kidney axis in IgAN development, we developed an orally administrated budesonide-encapsulated yeast microcapsules-based pectin gel, termed NYPs@Gel. Yeast microcapsules, compromising β-glucans and polysaccharides, Yeast microcapsules, comprising β-glucans and polysaccharides, protect budesonide from acidic degradation and promote its accumulation in gut-associated lymphoid tissue, thereby triggering mucosal immunity. The coated pectin gels prolong the formulation’s retention time in the intestines and provide sustained drug release. As anticipated, NYPs@Gel effectively enhances intestinal mucosa’s resistance to inflammation, reduces gut-derived IgA production, mitigates the side effects of budesonide, and restores gut microbiota balance. By modulating the gut-kidney axis, NYPs@Gel significantly improves IgAN outcomes, representing substantial advancements in the management and treatment of IgAN and a potential breakthrough in reducing the burden of chronic kidney disease.