The Effect And Mechanism Of Capparis Spinosa Water Extract On Gut Microbiota In Mice With Ulcerative Colitis

Ulcerative colitis(UC)is a chronic inflammatory disease characterized by inflammation of the mucosa of the colon and rectum with high morbidity.The conventional agents(aminosalicylic acid,corticosteroids,immunomodulators and monoclonal antibodies)currently used for ulcerative colitis usually have side effects and poor clinical efficacy,and there is a need to explore new drugs with better efficacy and tolerability.In this study,we investigated the effect of Capparis spinosa water extract(CSWE)on colonic histopathology,inflammation,microbial diversity and microbial metabolism of UC mice induced dextran sulfate sodium(DSS)by tissue section staining(HE,PAS),q RT-PCR,immunohistochemistry,16 S r RNA high-throughput sequencing,and non-targeted metabolomic approaches.The main results were as follows:(1)CSWE significantly ameliorated the symptoms of weight loss and colon shortening and reduced the disease activity index(DAI)score caused by DSS,significantly improved colonic shortening and colonic mucosal damage,reduced inflammatory infiltration,restored crypt and colonic glands,restored small intestinal villus length,and promoted nutrient absorption.(2)CSWE treatment improved colonic histopathology and increased the levels of tight junction protein genes(ZO-1)and occludin in intestinal epithelial cells in UC mice.CSWE also inhibited the expression levels of pro-inflammatory cytokines(TNF-α,IL-1β,IL-6 and IFN-γ)in colonic tissue.Furthermore,CSWE administration alleviated oxidative stress in the colon of DSS-induced UC mice,which was confirmed by the improvement in antioxidant enzyme activity and decrease in the malondialdehyde(MDA)level.(3)CSWE can increase the abundance and diversity of intestinal microorganisms and regulate the composition and structure of intestinal microorganisms,resulting in a significant increase in the abundance of probiotic Firmicutes and the number of Lactobacillus and Lachnospiraceae among intestinal microorganisms,and a decrease in the abundance of pathogenic bacteria Actinobacteria.(4)CSWE stimulates carbohydrate metabolic pathways for energy supply and glyoxalate and dicarboxylic acid metabolic pathways for anti-inflammation,resulting in metabolites that favor the restoration of intestinal inflammation,leading to a reduction in inflammation levels and weight restoration,there are three main groups of microorganisms that are closely related to metabolism,among which the Firmicutes is significantly more relevant to metabolism than other phyla.Results suggest that CSWE,a safe and effective natural plant-derived drug,may be an ideal product for the treatment of UC.However,the bioactive components of CSWE and its mechanism for treating UC need further purification and study.