A synergistic probiotic delivery strategy: Pectin-protein-hyaluronic acid hydrogel microcapsules enhance the protective efficacy of Lacticaseibacillus rhamnosus JY027 against DSS-induced colitis

Probiotics have shown potential in alleviating ulcerative colitis (UC) by modulating gut microbiota, restoring intestinal barrier integrity, and suppressing inflammatory responses. However, their oral efficacy is limited by poor gastrointestinal survival and insufficient colonic targeting. To address these limitations, a ternary hydrogel microcapsule (JYPWH) composed of apple pectin, whey protein isolate, and hyaluronic acid (HA) was developed to encapsulate Lacticaseibacillus rhamnosus JY027. As a dual-functional delivery system, JYPWH combined probiotic protection against gastrointestinal stress with HA-CD44-mediated delivery to inflamed colonic tissue. Oral administration of JYPWH significantly alleviated DSS-induced colitis in mice. Mechanistically, JYPWH promoted intestinal barrier repair by upregulating MUC-2, ZO-1, and Occludin. Concurrently, the NF-κB signaling pathway was suppressed in colonic tissue, serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were decreased, and serum levels of the anti-inflammatory cytokine IL-10 were increased. JYPWH also reduced inflammation-induced CD44 overexpression in colonic tissue. In addition, JYPWH reshaped the gut microbiota of DSS-treated mice by increasing beneficial taxa such as Lachnospiraceae_NK4A136_group and decreasing opportunistic pathogens, including Escherichia-Shigella , while restoring colonic short-chain fatty acid levels. Collectively, JYPWH integrates probiotic protection with HA-CD44-mediated colonic delivery, offering a promising strategy for UC intervention.