Molecular mechanisms of ameliorating DSS-induced ulcerative colitis mediated by human milk oligosaccharide 2′-fucosyllactose based on RNA-seq analysis

Abstract

Ulcerative colitis (UC) is a disease characterized by constant and ongoing inflammation. Previous studies had found that 2-Fucosyllactose (2′FL), a human milk oligosaccharide, can alleviate inflammation and regulate immunologic function. However, the molecular mechanism of 2′FL on dextran sulfate sodium (DSS)-induced colitis mice is not clear. Thus, in this study, the mechanism of 2′-FL against DSS-induced colitis in mice was investigated and verified by RNA-seq technology and molecular biology. 2′FL significantly improved the secretion of anti-inflammatory cytokines (IL-4 and IL-2) and blocked proinflammatory cytokines (MPO and IL-17), as well as with no side effects on organs. In addition, 2′FL exhibited protection effect mainly relation to regulate immune function and repressing TLR4/MAPK/NF-κB signaling pathways based on RNA-seq analysis. Furthermore, Western blot analysis and immunohistochemistry verified that 2′FL mitigated DSS-induced colitis via NF-κB and MAPK signaling pathways. These discoveries provided a possible mode for 2′FL in preventing and treating UC. Taken together, these findings demonstrate that 2′-FL alleviates ulcerative colitis via regulating immunity and repressing TLR4/MAPK/NFκB pathway, and this study may provide a new opinion for the study of UC drugs.