Oxidized Starch-Chitosan-Mg ²⁺ Gel Enhances Colonic Mg ²⁺ Absorption in Deficient Mice with Associated SCFAs and Transporter Modulation

Conventional magnesium supplementation relies on passive diffusion in the small intestine, resulting in poor bioavailability. To address this, we developed an oxidized starch-chitosan-Mg 2+ composite gel that directs more Mg 2+ to the colon, where resistant polysaccharides are fermented to SCFAs that may actively enhance absorption. Mg 2+ incorporation increased the gel’s resistant component to 52.42 ± 0.63%. Increasing Mg 2+ from 0.5% to 2% reduced cumulative upper gastrointestinal release from 70.61 ± 0.79% to 43.62 ± 1.01% ( p < 0.05), with higher concentrations showing no further improvement. In Mg 2+ -deficient mice, the gel dose-dependently restored serum Mg 2+ to healthy levels. Comparison at equal Mg 2+ doses revealed that the polysaccharide carrier independently contributed to enhanced absorption. Mechanistically, resistant polysaccharides were associated with upregulation of SCFAs receptors (FFAR2/FFAR3/HCAR2) and Mg 2+ transporters (TRPM6/TRPM7/CNNM4), with immunofluorescence indicating TRPM7 upregulation. This work provides proof-of-concept evidence for a paradigm shift from passive supplementation to active regulation via SCFAs-associated transporter modulation.