Functional And Mechanistic Investigation Of Alleviation Effect From Xylo-oligosaccharide On Acute Inflammatory Bowel Disease In Mice

Inflammatory bowel disease(IBD)is an intestinal inflammatory disease with a high incidence.One of its typical features is the reduction of intestinal Treg cells.Clinical data shows that by reinfusion of Treg cells can relieve the clinical manifestations of IBD to some extent.Studies have shown that dietary polysaccharides are first decomposed into oligosaccharides by the intestinal microflora in the body,and oligosaccharides are further decomposed to produce short-chain fatty acids(SCFAs),which promote the differentiation of intestinal Naive CD4~+T cells into Treg cells.Improve IBD.Xylo-oligosaccharide(XOS),which is widely used at present,can be metabolized by intestinal microbes to produce SCFAs.However,whether XOS can induce the production of Treg cells by producing SCFAs in vivo and thus alleviate the effects of IBD is not known.In this study,C57BL/6J mice were selected and acute IBD models in mice were obtained using the widely used Dextran sulphate sodium salt(DSS)induction method.This model was used to evaluate the effect of XOS in relieving IBD,and its mechanism was preliminary studied.In this study,We first use 2%,3%and 4%DSS solution drink feeding mice.During the7-day experimental period,all disease indicators of the mice were detected by means of regular sampling and final sampling.The experimental results showed that the three DSS concentrations in the diet increased the rate of weight loss,fecal occult blood positive,and accompanied by diarrhea.In addition,the length of the colon was shortened,the colon crypts disappeared,the goblet cells were severely damaged,and the mucosa was damaged.Intrinsic-layer has inflammatory cell infiltration.Among them,the indicators of 3%DSS drinking mice are most similar to the clinical manifestations,so we will use 3%DSS as the working concentration for follow-up studies.Second,XOS was used to drink mice on the basis of the obtained mouse IBD model to evaluate the alleviation effect of XOS on IBD.The experimental results showed that compared with DDW-treated IBD mice,XOS-treated IBD mice maintained body weight,improved fecal occult blood,and reduced diarrhea.Further examination of colon histopathological changes revealed that the colon length of XOS-treated IBD mice was maintained,the colon tissue structure was clear,the crypts were clearly visible,the destruction of goblet cells was reduced,and the inflammatory cell infiltration was reduced.In addition,XOS-treated IBD mice exhibited a very similar phenotype to normal mice.The above results fully demonstrate that XOS can relieve acute IBD in mice.It is known that XOS enters the body and can be metabolized into SCFAs by intestinal microbes,and SCFAs can increase the number of Treg cells.Therefore,the number of Treg cells in the Peyer's patches(PP),a major immune response site in the mouse intestine,was measured by flow cytometry.The experimental results showed that compared with normal mice and DDW-treated IBD mice,the number of Treg cells in intestinal PP of XOS-treated IBD mice was significantly increased.In addition,we also detected Treg cells in the body's largest peripheral immune organ spleen.The number of Treg cells has also increased significantly.The above experimental results suggest that XOS may relieve acute IBD in mice by increasing the number of Treg cells.Finally,since XOS can increase the content of SCFAs in the intestine,SCFAs(acetic acid,propionic acid and butyrate)were added under the in vitro experimental system in which the Naive CD4~+T cells of the mouse spleen were induced to differentiate into Treg cells.The results showed that propionic acid and butyrate could promote the differentiation of Treg cells in vitro.It is suggested that XOS may increase the number of mouse Treg cells by propionic acid or butyrate,which in turn relieves IBD.In summary,this study established a mouse acute IBD model and used this model to demonstrate that XOS can be effective relieve acute IBD in mice.Because XOS can be metabolized into SCFAs in the intestine,and XOS manifests itself in the body Similar to propionate and butyrate,it promoted the differentiation of Naive CD4+T cells into Treg cells.Therefore,we speculate that XOS is likely to promote Treg cell differentiation in the intestinal tract as SCFAs,which in turn may relieve a possible mechanism of IBD.This study provides an important preliminary experimental basis for the further exploration of the molecular mechanism of XOS in in vivo remission of IBD.