Low-Molecular-Weight Fucoidan from Undaria pinnatifida Mitigates Salmonella-Induced Injury Through Gut Microbiota and Immune Regulation

Salmonella primarily affects the gastrointestinal tract, causing local and systemic symptoms. Fucoidan exhibits therapeutic potential against Salmonella-induced pathology; however, the influence of its molecular weight on efficacy remains poorly understood. In this study, low-molecular-weight fucoidan from Undaria pinnatifida (LUPF) was prepared and characterized, and its protective effects against Salmonella infection were evaluated in a mouse model. LUPF effectively mitigated Salmonella-induced multiple organ damage by preserving mucin secretion and tight junction protein expression. Metabolomics analysis further demonstrated that LUPF normalized Salmonella-induced metabolic disturbances, thereby reducing systemic dysfunction. Mechanistically, LUPF suppressed inflammation by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, while alleviating oxidative stress through activation of the Nrf2 pathway. In addition, LUPF restored gut microbiota homeostasis by reducing Proteobacteria levels, improving the Bacteroidota/Firmicutes ratio, enriching beneficial taxa, and enhancing short-chain fatty acid production. In vitro experiments further revealed that LUPF attenuated Salmonella-induced inflammation by modulating macrophage polarization. Collectively, these results suggest that LUPF has promising potential as a prebiotic candidate for reducing the risk of Salmonella-associated diseases.