Human milk oligosaccharide 2′-fucosyllactose alleviates DSS-induced ulcerative colitis via improving intestinal barrier function and regulating gut microbiota

Abstract

Ulcerative colitis (UC) is an inflammatory disease with the process recurrent and chronic. Human milk oligosaccharide 2′ fucosyllactose (2′FL) possessed unique immune response and antioxidant activities, whereas its protective effect in colitis remains unexplored. Herein so as to track the beneficial effect of 2′FL in colitis, DSS-induced colitis was established and the inflammatory response, gut microbiota, intestinal tract barrier and molecular signaling pathway were measured. Results showed that 2′FL can alleviate the colitis symptoms, reduce the number of inflammatory cells, inhibit the overproduction of transforming growth factor (TGF)-β3 and tumor necrosis factor (TNF)-α, promote the production of anti-inflammatory cytokine such as interleukin-22 (IL-22) by TGF-β/SMAD2/SMAD3/SMAD4 pathways. Furthermore, 2′FL inhibited the production of lipopolysaccharide-binding protein (LBP) and lipopolysaccharide (LPS), restored intestinal barrier integrity by enhancing the levels of occluding, claudin-1, mucin mucin-2 (MUC-2), and zonulin occludin-1 (ZO-1) and further prevent harmful substance from escaping into the body, ultimately protected the liver against oxidative damage. Moreover, 16S rRNA Gene Sequencing analysis showed that 2′FL reversed the change of gut microbiota in colitis mice by reducing the abundance of the Bacteroides, Clostridium and Turicibacter, and enhancing the abundance of Coprococcus and Prevotella. In short, 2′FL supplementation could be a promising nutritional strategy for alleviating UC, and improving related diseases.