Postbiotic delivery via alginate encapsulation alleviates DSS-induced colitis by modulating gut microbiota and SCFA-mediated immune signaling.

Probiotic therapies for IBD are limited by low gastrointestinal viability and inconsistent efficacy. Postbiotics, non-viable microbes or their metabolites, offer a safer, more stable option, yet their distinct functions remain unclear, largely due to the lack of standardized delivery systems for direct comparison. In this study, we have developed a dual-delivery sodium alginate encapsulation system designed to facilitate the controlled gastrointestinal release of Lactiplantibacillus plantarum dy-1 in both its live (Sdy-1) and heat-inactivated (SHdy-1) forms. Employing colitis mouse model, we evaluated the effects of these formulations on inflammation, epithelial integrity, short-chain fatty acid (SCFA) production, and gut microbiota under equivalent delivery conditions. Both formulations were effective in mitigating colitis symptoms, SHdy-1 outperformed Sdy-1 and controls by significantly reducing disease activity (2.33 vs. 3.87), improving colon length (5.62 ± 0.33 cm VS 4.78 ± 0.44 cm), and suppressing pro-inflammatory cytokines TNF-α (decreased in 69.6 %), IL-6 (85.7 %), and IL-1β (55.4 %). It also enhanced SCFA levels, particularly butyrate (27.48 mmol/mg), and up-regulated SCFA-related receptors GPR41, GPR43, and PPARγ. Microbiota analysis showed higher α-diversity (Shannon index: 5.95 ± 0.35) and enriched beneficial genera including Bacteroides and Lachnospiraceae_NK4A136_group, while reducing the abundance of Escherichia-Shigella and Desulfovibrionaceae. This suggests alginate-encapsulated postbiotics like SHdy-1 offer effective anti-colitic effects by modulating immunity, metabolism, and microbiota, making it a promising candidate for IBD therapy.