| Ulcerative colitis is a common gastrointestinal disease.Its main characteristics are high morbidity,difficult to cure and easy to recur.Studies have shown that its etiology is related to environmental changes,intestinal microbiota imbalance,immune dysfunction and other factors.Live probiotics can maintain the balance of intestinal microbes,improve the immune function of the body and prevent ulcerative colitis.However,whether inactivated bacteria and their fermented products have a probiotic function for ulcerative colitis and its mechanism of action remains to be studied.In this study,dextran sodium sulfate was used to induce mice to establish an ulcerative colitis model,to explore the effects of inactivated Bifidobacterium animalis subsp.Lactis U9 fermented milk on tight junction proteins,inflammatory factors and intestinal flora in mice,and to evaluate the preventive effect of inactivated U9 on ulcerative colitis,ultimately provides theoretical guidance for the development and application of fermented products of inactivated probiotics,as well as the alleviation and treatment of ulcerative colitis.Forty 8-week-old wild-type male mice were randomly divided into control group,model group,inactivated U9 low-dose group,and inactivated U9 high-dose group.The control group was intragastrically administered with normal saline during the test period(14 days);0-7 days,the model group was intragastrically administered with normal saline,and the inactivated U9low-dose group and inactivated U9 high-dose group were intragastrically administered with U9at a concentration of 1.6×10~9 CFU/m L,8.0×10~9 CFU/m L of fermented milk with inactivated bacteria,the gavage dose is 0.1m L;8-14 days,the model group can drink 2.5%(w/v)dextran sodium sulfate solution freely while gavage with normal saline.U9 low-dose group,U9 high-dose group drink dextran sodium sulfate solution while gavage the fermented milk of corresponding concentration.After the modeling,the mouse disease activity index,inflammatory factor levels,tight junction protein expression and intestinal microbial composition were tested.The results showed that the weight of the mice in the control group continued to increase during the modeling period,and the mice were in a healthy state;the weight of the other three groups of mice increased in the first 3 days of modeling and decreased from the fourth day,and the decrease in the inactivated U9 group was smaller than that of the model group.The disease activity index of the model group was significantly higher than that of the control group(P<0.05),and the mice were successfully modeled;the score of the inactivated U9 fermented milk group was significantly lower than that of the model group(P<0.05).Compared with the model group,the colon length in the inactivated U9 group was significantly increased(P<0.05),the colonic histopathological score was significantly reduced(P<0.05),and the high-dose group both returned to the normal group level.In addition,the expression of colonic pro-inflammatory factors(TNF-?,IFN-?,IL-6)in the inactivated U9 group decreased,and the expression of anti-inflammatory factors(IL-4,IL-10)and tight junction proteins(ZO-1,Occludin),E-cadherin)at the m RNA level increased,immunohistochemical coloration deepened and score increased.Diversity analysis of intestinal flora showed that the Alpha diversity indexes Shannon,Ace,Chao of the high and low dose U9 groups increased,while Simpson decreased.The microbial composition in the PCo A results was different from the model group,indicating that the diversity and richness of the intestinal flora were higher than that in the model group.After the intervention of inactivated U9 fermented milk,the relative abundance of Firmicutes,Cyanobacteria,Verrucomicrobia and Deferrobacteria increased,and the relative abundances of Bacteroides and Tenericutes decreased;in addition,U9 effectively increased the beneficial bacteria(Ruminococcaceae?UCG-014,Prevotellaceae?UCG-001,Lactobacillus)in the intestines,and reduces the harmful bacteria(Lachnospiraceae?NK4A136?group,Erysipelatoclostridium).Correlation analysis results showed that Roseburia,Prevotellaceae?UCG-001 and Muribaculum were positively correlated with anti-inflammatory factors and negatively correlated with pro-inflammatory factors;Erysipelatoclostridium,unclassified?o??Bacteroidales,Bacteroides and Helicobacter were negatively correlated with anti-inflammatory factors and positively correlated with pro-inflammatory factors.In summary,inactivated Bifidobacterium animalis subsp.Lactis U9 fermented milk achieves the goal of preventing ulcerative colitis by up-regulating tight junction proteins,inhibiting inflammation,and regulating intestinal flora. |
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