Fucoidan alleviates Salmonella-induced inflammation and mortality by modulating gut microbiota and metabolites, protecting intestinal barrier, and inhibiting NF-κB pathway

Abstract

Salmonella typhimurium (ST) poses a serious threat to host health, and the adverse effects of antibiotic treatment necessitate the urgent search for innovative therapies to complement antibiotic treatment. This study indicated that high dosage of Undaria pinnatifida fucoidan (UPF) protected against mortality in mice infected with ST. UPF decreased the number of ST in the liver, reduced organ indexes, and increased colon length, indicating its protective effect against ST infection. UPF reduced the disruption of the intestinal barrier induced by ST, as evidenced by reduction in the loss of crypts and colonic mucus layer and inflammatory cell infiltration, as well as increases in the levels of tight junction proteins. UPF reduced oxidative stress and inhibited the NF-κB signalling pathway, alleviating inflammatory response. The protective effect of UPF against ST infection can be closely associated with modulation of the gut microbiota, e.g. a reduction in Proteobacteria and increases in Lactobacillus and Akkermansia. In addition, UPF modulated ST-induced alterations of microbiota metabolites and affected various metabolic pathways that crucial to host health, primarily involving a reduction in lactate and increases in secondary bile acids and short chain fatty acids. This study suggests that UPF can confer benefits in pathogen-induced diseases by modulating the gut microbiota and metabolites and protecting the intestinal barrier function.