β-Glucan-based superabsorbent hydrogel ameliorates obesity-associated metabolic disorders via delaying gastric emptying, improving intestinal barrier function, and modulating gut microbiota.

The global obesity epidemic and its associated metabolic syndrome highlight the urgent need for new weight-loss therapies that provide high efficacy and patient compliance. Herein, we propose a novel, noninvasive approach using an orally administered β-glucan-based superabsorbent hydrogel (βC-MA hydrogel) to improve obesity-associated metabolic disorders. Results demonstrated that βC-MA hydrogel functioned as a dynamic exoskeleton within the gastrointestinal tract, slowing gastric emptying and reducing the digestion and absorption of ingested food. Furthermore, βC-MA hydrogel alleviated hepatic lipid accumulation and prevented hepatic steatosis and fibrosis by regulating the expression levels of key genes involved in lipid metabolism, including Cd36, SREBP 1c, FAS, ACC1, Cpt1a, and HSL, thereby limiting the progression of nonalcoholic fatty liver disease. In addition, βC-MA hydrogel reduced intestinal inflammation by lowering tumor necrosis factor-α and interleukin-6 levels while enhancing gut barrier function through increased expression of claudin-1, ZO-1, and MUC2. Finally, βC-MA hydrogel, enriched with obesity-negative probiotics such as Akkermansia, norank_f__Muribaculaceae, and Faecalibaculum, promoted the production of short-chain fatty acids. Consequently, βC-MA hydrogel significantly reduced body weight and fat accumulation and improved blood glucose and lipid levels, with efficacy comparable to semaglutide therapy and superior to β-glucan and sodium carboxymethylcellulose interventions. Overall, these findings suggest that βC-MA hydrogel could serve as a promising next-generation ingestible medical device for alleviating diet-induced obesity and related metabolic disorders by modulating food digestion and absorption, improving intestinal inflammation and barrier function, and regulating gut microbiota composition.