Changes Of Intestinal Flora And Its Relationship With IL-23/IL-17 Axis In Patients With Ulcerative Colitis

Background The etiology and pathogenesis of ulcerate colitis(UC)are still not completely elucidated so far,and it is generally accepted that there are many factors such as environmental factors,genetic predisposition,intestinal barrier dysfunction,immune dysfunction and other factors Chronic inflammatory response and immune response disorder are the key pathological stages of UC.Intestinal flora disturbance is an important factor in the changes of inflammatory response and immune response,which is an important factor of UC pathology.Objective To investigate the changes of intestinal flora distribution and its relationship with IL-23 /IL17 in the UC patients.Methods The fresh fecal samples from 20 patients with active UC and 20 healthy controls were collected.The distribution of the flora was analyzed by direct smear and traditional bacterial culture.The changes of bacteria were detected by real-time PCR.The hemoglobin,albumin,erythrocyte sedimentation,and C-reactive protein levels were tested routinely.Both normal and damaged mucosal tissues of UC patients were examined and obtained by colonoscopy,and further assessed by Mayo score,Baron grading,and HE staining.The expression of IL-17 and IL-23 was observed by immunohistochemistry and Western blot.Results(1)The degree of flora imbalance in active UC patients was higher than that in the controls(P<0.05).(2)The results of aerobic culture showed that the number of Escherichia coli in the UC patients was significantly lower than that in the normal controls(P<0.01),while Enterococcus was increased obviously(P<0.01).The results of Anaerobic culture revealed that the number of bacteria in Bacteroidetes,Bifidobacterium bifidu and Lactobacilli was significantly decreased(P<0.01).(3)Quantitative analysis of target bacteria showed that the relative quantification of Escherichia coli,Bacteroidetes,Bifidobacterium bifidu and Lactobacilli in the UC patients was significantly lower than those in the normal subjects,and the number of Enterococcus was significantly increased(P<0.01).(4)Compared with control group,no significant change of hemoglobin in the UC patients was ovserved,but albumin was significantly decreased(P<0.05),erythrocyte sedimentation,and C-reactive protein levels were enhanced obviously(P<0.01).(5)The Mayo score,Baron grading,and histopathological score were all increased(P<0.01).(6)High levels of IL-17 and IL-23 expressions were detected in the UC patients(P<0.01).(7)Correlation analysis showed that the average optical density value of IL-17 and IL-23 expression was positively correlated with Baron grading(r=0.717,P=0.02;r=0.849,P=0.016)and pathological score(r=0.660,P=0.03;r=0.675,P=0.032)respectively.Meanwhile,the average optical density value of IL-23 expression was negatively correlated with the number of Escherichia coli(r=-0.699,P=0.025),and positively correlated with Enterococcus(r=0.872,P=0.010).Furthermore,the average optical density value of IL-17 expression was positively correlated with Enterococcus(r=0.764,P=0.046),and both of them were not correlated with other flora.Conclusion Obvious flora imbalance exists in active UC patients,changed intestinal microflora is closely related with the degree of inflammation.IL-23/IL-17,works as a key factor in the development of UC,may be related to the changes of intestinal microflora,the interaction between intestinal microflora and IL-23/IL-17 plays an important role in the pathogenesis of UC.