A precision-engineered chitosan alleviates gastric ulcers and restores gut microbiota homeostasis in rats: Dual mechanisms of mucosal barrier fortification and oxidative stress mitigation.

This study innovatively explored chitosan by engineering a monodisperse formulation with a precisely adjusted molecular weight, thereby establishing a reference benchmark. The molecular architecture of chitosan was comprehensively characterized using PMP-HPLC, SEM, FT-IR, and XRD, offering detailed insights into its monosaccharide composition, morphology, functional group composition, and crystalline structure. A 70 % ethanol-induced acute gastric ulcer model in rats was used to evaluate the chitosan's functions. The bioactivities of chitosan were characterized using macroscopic, oxidative stress, immunology, barrier function, cytokine analyses, and gut microbiota, and the findings extended current understanding in the field. Chitosan could prevent gastric mucosal injury, as evidenced by reduced ulcer area (CHI-H, 1.37 % vs. MC, 75.0 %) and enhanced epithelial integrity (CHI-H, 90.2 % vs. MC, 40.2 %). The study also demonstrated that chitosan treatment increased levels of the SOD and GSH levels, normalized MDA levels, modulated gut microbiota, and restored the immune function. Additionally, it significantly reduced the expression levels of barrier indicators (COX-2/PGE2 and MPO/iNOS axes, 5.69 %-45.8 %), proinflammatory factors (IL-12, IL-1β, TNF-α, and IFN-γ; 2.55 %-27.3 %) in a dose-dependent manner. This suggested that NF-κB/MAPK signaling was involved in the chitosan's mechanism of action. Overall, this study established an innovative framework for designing chitosan-based biomaterials, highlighting its research and utilization significance, as well as paving the way for future exploration.