Immunological mechanisms of fecal microbiota transplantation(FMT)in treatment of dextran sulfate sodium(DSS)induced ulcerative colitis(UC)
Objective To analyze the therapeutic effect of fecal microbiota transplantation(FMT)on dex-tran sulfate sodium(DSS)induced ulcerative colitis(UC)mice and explore the relevant immunological mechanisms.Methods A total of 60 C57BL/6J mice were randomly selected,with 10 mice used for fecal collection(did not participate in the subsequent experiments),and the remaining 50 mice randomly divided into 3 groups:blank group(10 mice),which received normal diet and free access to sterile distilled water;model group and research group(20 mice each),in which ulcerative colitis(UC)mouse model was suc-cessfully established using dextran sulfate sodium(DSS).Model group and research group were allowed to freely drink a 2％dextran sulfate sodium(DSS)solution from the first day of self-grouping,to induce the formation of ulcerative colitis mouse model.After the mouse animal model was established,the model group was given saline enema,and the research group was given normal mouse fecal suspension saline mixfure enema twice,with a time interval of 3 days.On the second day after the completion of the second enema,all mice were euthanized and serum samples were collected.The expression levels of cell factors such as TNF-a,IL-6,IL-35,IL-22,IL-17 and soluble Fas in serum were determined using ELISA.The pathological morphology of the ulcerative colitis lesion in the colon tissue was observed by HE staining of the specimens,and the intestinal microbiota values and B/E values were quantitatively detected using the Jap-anese Oka intestinal microbiota analysis method.Results ELISA testing indicated that compared to blank group,model group and study group showed upregulation of TNF-a,IL-6,IL-17 and IL-22 levels,while IL-35 and soluble Fas levels were decreased(P＜0.05).Compared to the model group,the study group showed downregulation of TNF-a,IL-6,IL-22 and IL-17 levels,with an increase in IL-35 and soluble Fas levels(P＜0.05).Histopathological analysis of colon tissues showed that compared to the blank group,the model group displayed varying degrees of thinning of the mucosa,loss of epithelial structure,irregular distribution of glands,congestion and edema in the submucosal layer,along with significant infiltration of inflammatory cells,congestion of capillaries,obvious dilation of lymphatic vessels and diffuse distribution of small ulcers.The degree of colonic mucosal lesions in the study group mice was reduced compared to the model group,but partial mild dilation of lymphatic vessels and infiltration of a small amount of inflam-matory cells could still be observed.Analysis of bacterial flora showed that compared to the blank group,the model group and the study group showed significantly increased levels of intestinal bacteria,enterococ-ci,pseudomonas and clostridium,with a decreased B/E value(P＜0.05).Compared to the model group,the study group showed a significant increase in the levels of yeast,bifidobacteria and lactobacilli,with an increased B/E value(P＜0.05).Conclusion Fecal microbiota transplantation can improve the pathologi-cal damage of colonic tissue in UC mice and the structure of the intestinal microbiota in mice,reduce the expression of pro-inflammatory factors,promote the generation of anti-inflammatory factors,regulate in-testinal immune balance and promote intestinal mucosal repair.
fecal microbiota transplantationulcerative colitisimmunologymechanism research
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维普
