Fuc-S—A New Ultrasonic Degraded Sulfated α-l-Fucooligosaccharide—Alleviates DSS-Inflicted Colitis through Reshaping Gut Microbiota and Modulating Host–Microbe Tryptophan Metabolism

Scope: The dysbiosis of intestinal microecology plays an important pathogenic role in the development of inflammatory bowel disease. Methods and Results: A polysaccharide named Fuc-S, with a molecular weight of 156 kDa, was prepared by the ultrasonic degradation of fucoidan. Monosaccharide composition, FTIR, methylation, and NMR spectral analysis indicated that Fuc-S may have a backbone consisting of →3)-α-L-Fucp-(1→, →4)-α-L-Fucp-(1→ and →3, 4)-α-D-Glcp-(1→. Moreover, male C57BL/6 mice were fed three cycles of 1.8% dextran sulfate sodium (DSS) for 5 days and then water for 7 days to induce colitis. The longitudinal microbiome alterations were evaluated using 16S amplicon sequencing. In vivo assays showed that Fuc-S significantly improved clinical manifestations, colon shortening, colon injury, and colonic inflammatory cell infiltration associated with DSS-induced chronic colitis in mice. Further studies revealed that these beneficial effects were associated with the inhibition of Akt, p-38, ERK, and JNK phosphorylation in the colon tissues, regulating the structure and abundance of the gut microbiota, and modulating the host–microbe tryptophan metabolism of the mice with chronic colitis. Conclusion: Our data confirmed the presence of glucose in the backbone of fucoidan and provided useful information that Fuc-S can be applied as an effective functional food and pharmaceutical candidate for IBD treatment.