Fabrication and characterization of astaxanthin-loaded nanoprobiotic and its role in alleviating hyperuricemia via the regulation of the gut-kidney axis

Abstract

Hyperuricemia (HUA), a global metabolic disorder, is primarily managed through conventional pharmacotherapy. Many bioactive substances, e.g. astaxanthin (ATX) and probiotics, have great potential in ameliorating HUA, but their applications face some challenges, such as loss of activity. In this study, ATX-loaded nanoparticle was adsorbed onto the surface of tannic acid-Fe³⁺-coated Lactobacillus rhamnosus (LGG), followed by hyaluronic acid coating to obtain a nanoprobiotic system, LGG@MNH. In vivo and in vitro models demonstrated that LGG@MNH exhibited enhanced stability under various adverse conditions and improved adhesion characteristics in the intestine. Mice experiment revealed that LGG@MNH alleviated HUA symptoms and inflammatory responses in the kidneys. LGG@MNH increased gut microbiota diversity, beneficial bacterial populations, and short-chain fatty acid levels, thereby protecting the intestinal barrier function. These alterations ameliorated HUA-induced abnormalities in serum metabolite profiles, particularly amino acid, pyrimidine, and purine metabolism, which are closely associated with the kidney health. Furthermore, LGG@MNH regulated the expression of genes related to uric acid (UA) reabsorption and excretion in the kidney and intestine, thereby reducing serum UA levels. This study suggests that LGG@MNH holds superior potential for managing HUA and may serve as a promising strategy for its long-term treatment.