| Background:Compared with healthy subject,IBD patients have altered microbiota in their intestines and faeces,with fewer bacteria producing short-chain fatty acids(SCFAs).Studies have shown that the levels of fecal SCFAs were decreased significantly in active IBD patients.SCFAs are an important energy source for intestinal epithelial cells and that could enhance the functions of intestinal barrier.Recent studies have suggested that SCFAs,especially butyric acid,play an important immunomodulatory function.Farnesoid X receptor(FXR)in intestinal epithelial cells could sense the level of intracellular bile acid,and participate in intestinal bile acid metabolism and integrity maintenance of intestinal barrier.FXR is closely related to intestinal immunity,and plays an important role in regulating mucosal immunity.Studies have shown that the expression level of intestinal FXR in IBD patients is lower than that in normal subjects.Experimental results in mouse model of inflammatory bowel disease suggest that the use of FXR agonist can reduce intestinal inflammation.Decreased butyric acid and FXR expressions are simultaneously detected in IBD patients,suggesting that there might be some relationship between them.Whether butyric acid has an effect on the expression of intestinal FXR remains to be further studied,which may help broaden the treatment of IBD.Aims : The aims of study were to investigate the effect of butyrate on intestinal inflammation in IBD model and on FXR expression in intestinal epithelial cells.Methods:A total of 40 male C57BL/6J mice were randomly divided into 4 groups: A. normal control group,B.colitis model group,C.butyrate treatment group,D.butyrate + obeticholic acid treatment group.Each group was 10 mice.The normal control group was free to drink water,and the other three groups were free to drink 3% DSS solution to prepare colitis models.The colitis model group were received intragastric administration of saline at 20ml/Kg once a day.Group C were received intragastric administration of 0.5% sodium butyrate solution at 20ml/Kg once a day.Group D were received intragastric administration of 0.5% sodium butyrate with 0.025% obeticholic acid solution at 20ml/Kg once a day.After treated for 7 days,the indictors of state,diet,feces and activity of the mice were observed.Also,they got weighed daily.On the 8th day,blood was taken from the eyeballs of anesthetized mice,and serum was collected after centrifugation.ELISA was carried out to detect the IL-1? level.The length of colon was measured after the mice were killed and the same segments of the intestine were cut for HE staining and immunohistochemistry(IHC)to detect the FXR expression in colon.RT-PCR was used to detect the expression of FXR m RNA.The spleens were taken out to extract mononuclear cell for analyse of Treg/Th17 proportions by flow cytometry.Results:IHC indicated that the FXR expression in the colitis group decreased compared with the normal control group.Real time PCR and IHC showed that the FXR expression in the butyrate treatment group was higher than that of the colitis model group.Compared with the colitis model group,the butyrate treatment group had milder symptoms,milder intestinal lesions and lower levels of proinflammatory factor IL-1?in serum.Compared with the group treated with butyrate alone,the group treated with butyrate with obeticholic acid had higher Treg/Th17 ratio and lower levels of IL-1?.Conclusions:The expression level of intestinal FXR is decreased during intestinal inflammation.Butyric acid could promote the expression of intestinal FXR and alleviate DSS induced colitis in mice treated with FXR agonist.The mechanism might be related to regulating the balance of Treg/Th17. |
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