Abnormal Changes Of Intestinal Motility And Enteric Glial Cells In Ulcerative Colitis And The Effect Of Soluble Dietary Fiber

Background:Ulcerative colitis(UC)is a chronic non-specificity inflammatory bowel disease that was often located in colon and rectum,and its etiology has not been known clearly.Patients of UC often couple with gastrointestinal dysmotility and intestinal inflammation,which influence with each other,resulting in exacerbation of intestinal inflammation and gastrointestinal dysmotility,causing clinical management more difficult.The etiology and pathogenesis of UC is still unclear,and previous studies have shown that hereditary susceptibility,imbalance of intestinal flora,immunologic dysfunction and the changes of environment are risk factors.In recent years,studies found that enteric glial cells(EGCs)play an important role in the inflammatory activity of UC.Meanwhile,studies also found a possible active role of EGCs in the pathophysiology of gastrointestinal motor activity.Soluble dietary fiber(SDF),which was metabolized by intestinal microbiota into short chain fatty acid(SCFA)in the colon,could reduce the permeability of the colonic mucosa and maintain the stability of the intestinal mucosal barrier,and attenuate the intestinal inflammation of UC.However,the role of EGCs in intestinal dysmotility of UC and the effect of SDF on ECGs was still unclear.Objective:The purpose of the present study was to explore the intestinal motility and EGCs alteration on UC,and to investigate the effect of soluble dietary fiber on intestinal motility and EGCs.Also,the potential mechanism of SDF will also be investigated.Materials and methods:The experimental animals were male wild type C57BL/6 mice;colitis was induced by dextran sulfate sodium(DSS).The mice were randomly divided into four groups:normal group,DSS group,pectin group and pectin + antibiotics group.All the mice were fed ad libtum for 1 week before experiment.During the experiment,the normal group drink water freely,the DSS group was given 5%DSS solution for 7 consecutive days,for the pectin group,4%pectin was given for 4 weeks prior to DSS treatment,for the pectin + antibiotic group,4%pectin combined with antibiotics were given for 4 weeks,then 5%DSS for 7 days.Stool characters,fecal occult blood and body weight of the mice were regularly observed in each group during the sixth week,then the disease activity index score(DAI)were evaluated.Colonic transit time in each group was evaluated through the bead expulsion assay the day before and end of inducing colitis.After sacrificing the mice,the colon tissue was fitted into stationary solution to assess the contraction intensity and frequency.Also,HE staining was performed.Expression level of inflammatory factors(TNF-?,IL-1? and PGE2)was detected by enzyme-linked immunosorbent assay(ELISA),abnormalities of EGC was quantitatively and qualitatively analyzed by immunofluorescence and western blot.Results:Compared with normal group,colonic transit time of DSS group was significantly increased,while the transit time of pectin group and pectin + antibiotic group was significantly lower compared to DSS group.Body weight in DSS group had a significant drop,which was ameliorated by oral pectin.DAI score of pectin group and pectin + antibiotics group was significantly lower compared to DSS group.HE staining showed that the level of inflammation was relieved in the pectin and pectin +antibiotic group compared to DSS group,and ELISA assay revealed that the level ofTNF-?,IL-1? and PGE2 increased notably in DSS group,and after treatment with pectin,the level was decreased.The results proved that pectin ameliorated colonic inflammation of DSS induced-colitis.Compared with normal group,both the colonic contraction intensity and frequency were significantly decreased in DSS group,while pectin could improve the result.Immunofluorescence and western blot showed that the level of S100B and GFAP significantly increased in the DSS group,which indicated that the EGCs were abnormally activated.After treatment with pectin,the abnormal activation of EGCs was inhibited.Our experiment demonstrated that soluble dietary fiber could regulate intestinal dysmotility through EGCs in DSS induced colitis.Western blot and immunofluorescence showed that the connexin-43 was significantly decreased in DSS group,while pectin could increase its expression and promote intestinal motion.Conclusions:Intestinal motility and EGCs were abnormal activated in DSS induced-colitis model,soluble dietary fiber can regulate the abnormalities of colon movement through inhibition of EGCs abnormal activation,and the potential mechanism of SDF may be mediated through regulation of connexin-43 in EGCs.