Thiol-modified hyaluronic acid/l-glutamine crosslinked hydrogel: A redox-sensitive system for probiotic synergistic alleviation of DSS-induced colitis in mice.

HA-SH-L-P is a novel redox-responsive hydrogel delivery system designed to enhance probiotic colonization, survival, and targeted delivery in the gastrointestinal tract through the synergistic interaction between l-glutamine and probiotics. This interaction not only improves probiotic viability but also modulates the immune microenvironment and strengthens intestinal barrier function. Using Limosilactobacillus fermentum CECT5716 as a model strain, the hydrogel demonstrated stable mechanical properties and responded to hydrogen sulfide (H₂S) in the intestinal microenvironment, enabling rapid probiotic release. In vitro, HA-SH-L-P significantly increased probiotic survival (by 3.56 log CFU/mL compared to free strains). In vivo, HA-SH-L-P modulated immune responses, maintained intestinal barrier integrity, and stabilized the gut microbiota. These results highlight the exceptional performance of HA-SH-L-P as a probiotic delivery system, offering a new approach for the treatment of related diseases.