Neuroprotective effect of fucoidan by regulating gut-microbiota-brain axis in alcohol withdrawal mice

Abstract

• Fucoidan could alleviate the depression-like behaviors in chronic alcohol exposure and withdrawal mice. • Fucoidan inhibited alcohol-induced microglia cell activation and inflammation in brain through the TLR4/MyD88/NF-κB p65 signaling pathway. • Fucoidan could regulate the gut flora of mice exposed to alcohol. The aim of the study was to detect the neuroprotective activity of fucoidan in alcohol exposure and withdrawal mice and the underlying mechanisms. C57BL/6J mice were used to establish the murine model of chronic alcoholism and withdrawal over 10 weeks of alcohol exposure. After fucoidan treatment, the depression-like behaviors in mice with alcoholism were improved, and 5-hydroxytryptamine and brain derived neurotrophic factor levels were increased both in serum and brain tissues. Fucoidan treatment attenuated the increase of lipopolysaccharide induced by alcohol, and decreased tumor necrosis factor-α and interleukin-1β levels. In hippocampus fucoidan inhibited microglia cell activation, and down-regulated the levels of Toll-like receptor 4 and its downstream protein factors. In addition, fucoidan regulated the structure of gut flora and made the composition of microbiota more similar to that of the normal control mice with increased abundances of Prevotella and Alloprevotella . Oral administration of fucoidan could alleviate the depression-like behaviors of mice with alcoholism through the gut-microbiota-brain axis.