摘要
Ulcerative colitis(UC)is a public health concern.The quest for drugs characterized by minimal side effects and optimal safety profiles for managing UC has emerged as a primary research topic.Recent evidence suggests the efficacy of Lactobacillus-derived exopolysaccharides containing mannose(MnEPSs)in alleviating UC.Lactoba-cillus could not synthesize MnEPSs in the glucose-only MRS medium,but with mannose added to the carbon source,MnEPSs were produced directionally,of which mannose accounts for 5.9-7.8%of the total sugar content.Subsequently,MnEPS-6M3,MnEPS-Q5M22,MnEPS-D4L1,and MnEPS-CCFM 1393 were used to investigate the mechanism of UC relief.The results showed that compared with non-MnEPSs,MnEPSs had the better effect on reliving UC.Phenotypically,four MnEPSs alleviated weight loss,DAI score,crypt disappearance,inflammatory cell infiltration,and mucosal edema of UC in mice.Mechanistically,MnEPSs increased the expression of ZO-1 by 52.38-115.87%to repair intestinal barrier,inhibited inflammatory factors(TNF-α,IL-1β,IL-6,IFN-γand IL-17)and increasd anti-inflammatory cytokines(IL-10)by reducing colonic F4/80^(+)macrophages(decreased 4.34-7.01%)and colonic iNOS^(+)M1 macrophages(decreased 7.3-10.52%),and promoted the production of acetic acid(increased 153.21-226.93%),propionic acid(increased 360.71-528.57%),and butyric acid(increased 127.45-156.86%)in cecal contents.Interestingly,MnEPS-Q5M22 and MnEPS-CCFM 1393 increased the abundance of butyric acid-producing Dunaliella.In summary,this study provides a theoretical basis for the directional synthesis of functional MnEPSs.
基金
supported by the National Key Research and Development Program of China(NO.2022YFF1100203).
