Porous-starch-encapsulated quercetin remodels the gut microbiota and elevates short-chain fatty acids, alleviating hyperglycaemia-associated phenotypes in T2DM mice.

INTRODUCTION: Quercetin (QUE), a plant-derived flavonoid abundant in many vegetables, has been implicated in glycaemic regulation; however, its application in functional foods is limited by poor stability during upper-gastrointestinal transit and low oral bioavailability. This study aimed to develop a porous-starch-based delivery system to improve the bioavailability and metabolic benefits of QUE. METHODS: Porous-starch-encapsulated quercetin microspheres (PSQ) were engineered using corn-derived porous starch as a carrier. The in vitro release behavior of PSQ was evaluated under simulated gastric and intestinal conditions. The metabolic effects of PSQ were further investigated in a type 2 diabetes mellitus (T2DM) mouse model by comparing PSQ with free QUE. Glucose metabolism, lipid metabolism, gut microbiota composition, and caecal short-chain fatty acids (SCFAs) were systematically analyzed. RESULTS: In vitro, PSQ showed restrained release under gastric-like conditions but enhanced release under intestinal-like conditions, indicating reduced premature release and improved intestinal-phase availability. In T2DM mice, PSQ administration improved body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), serum glycated protein (GSP), and HOMA-derived indices of islet function, while partially alleviating serum and hepatic lipid abnormalities. The higher PSQ dose exhibited stronger effects than the lower dose and free QUE. Microbiota analysis revealed PSQ-associated enrichment of beneficial metabolic-related genera, including Lactobacillus, Adlercreutzia, and Limosilactobacillus, together with depletion of taxa such as Lawsonibacter and Bilophila. These microbial alterations were accompanied by increased caecal SCFA levels, which were significantly correlated with glycaemic and biochemical parameters. Correlation-network analysis identified Turicimonas and Muribaculum as potential microbial signatures associated with metabolic regulation. DISCUSSION: Porous-starch encapsulation provides partial gastric protection and enhances intestinal availability of quercetin, thereby potentiating its metabolic benefits in T2DM mice. The improved metabolic outcomes were accompanied by coordinated modulation of gut microbiota and SCFA production, supporting PSQ as a promising strategy for developing QUE-based functional food interventions.