Sargassum fusiforme-derived Exosome-like Nanoparticles Suppress TLR4/MyD88/NF-κB Pathway to Alleviate Colitis via Modulating Gut Microbiota.

Plant-derived exosome-like nanoparticles (PELNs) offer both prophylactic and therapeutic potential for ulcerative colitis (UC). Following the successful isolation of Sargassum fusiforme-derived exosome-like nanoparticles (SELNs), this study investigated the protective efficacy of SELNs in mitigating Citrobacter rodentium-induced colitis. SELNs administration exhibited prolonged gut retention and colon-targeting efficacy and significantly alleviated colitis symptoms, including body weight loss, colonic shortening, and histological damage, while promoting tight junction and MUC2 protein expression. SELNs suppressed the TLR4/MyD88/NF-κB cascade, a key inflammatory pathway, resulting in downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and upregulated anti-inflammatory cytokines (IL-10, IL-22), coupled with iNOS abrogation. Furthermore, SELNs modulated the gut microbiota compositon, especially increasing the abundance of Muribaculum intestinale, and promoted the production of short-chain fatty acids (SCFAs). Collectively, these findings suggest that SELNs possess significant promise as a functional food ingredient for colitis through intestinal homeostasis modulation and inflammatory pathway regulation. Given their natural source and potent anti‑inflammatory effects, SELNs hold good potential for commercialization as a novel nutraceutical for inflammatory bowel disease intervention.