Abstract

Probiotics help treat ulcerative colitis (UC) by stabilizing gut microbiota, strengthening the mucosal barrier, and modulating immune responses, yet their viability plummets in the harshly acidic stomach. To overcome this limitation, we engineered a colon-targeted, double-layer oral delivery system in which Lactobacillus plantarum (LP) is first adsorbed onto porous maize starch (PMS) and subsequently coated with calcium-cross-linked alginate to form microgels (LP@aPMS). Scanning electron microscopy and confocal laser scanning microscopy confirmed that the dense alginate shell tightly enveloped PMS, shielding LP from gastric erosion. In dextran sulfate sodium-induced colitis mice, oral administration of LP@aPMS markedly improved clinical outcomes, characterized by reduced disease-activity index and rectal bleeding scores, mitigated colonic shortening and body-weight loss, and increased overall survival rate. Mechanistically, LP@aPMS elevated the anti-inflammatory cytokine IL-10 and significantly suppressed pro-inflammatory mediators (TNF-α, IFN-γ, IL-6, IL-1β), thereby reversing DSS-induced histopathological damage in colonic tissue. These results demonstrate that PMS-based bilayer microgels provide effective gastric protection, targeted intestinal release, and potent therapeutic benefits, laying an experimental and technological foundation for next-generation probiotic microgel preparations.