Preventive Effect And Intestinal Microecological Improving Of Probiotic Agent R1 Fermented Camel Milk On Ulcerative Colitis In Mice

Ulcerative colitis(UC)is a chronic,non-specific,recurrent disease that is difficult to cure,has a high cancer rate,has no specific drugs,and is increasing year by year,posing a potential threat to human health.Therefore,it is important to explore the methods of its treatment and prevention.Many studies have shown that ulcerative colitis was mainly caused by unstable intestinal flora,immune imbalance,genetic susceptibility and poor lifestyle.Currently,glucocorticoids,immunosuppressants,aminosalicylates and biologics are used clinically to treat UC.Probiotics and camel milk are also complementary treatments for ulcerative colitis.However,the possible role of the complex probiotic R1 fermented camel dairy products in the prevention of ulcerative colitis and its potential mechanisms have not been yet clear.In this pepar,we studied the preventive effect of probiotic agent R1 fermented camel milk on DSS-induced ulcerative colitis and intestinal microecological improving of mice which laid the foundation for exploring probiotics and fermented camel milk as new UC supplements.In this pepar,forty SPF grade C57BL/6J female mice were randomly divided into four groups: control group(CK),model group(DSS),camel milk group(TC),and fermented camel milk group(FTC).During the first 21 days of the test period,the control and model groups were gavaged with 0.1 m L of sterile saline,the camel milk group with 0.1 m L of sterilized camel milk,and the fermented camel milk group with 0.1m L of probiotic R1 fermented camel milk,during which all four groups of mice were free to drink distilled water.dextran sodium sulfate solution.During the test,the body weight loss rate of mice was calculated,fecal properties were observed,and fecal occult blood was detected,which led to a comprehensive assessment of the disease activity index of mice.At the end of the experiment,pathological differences were analyzed in colon tissue using HE staining method,the content of inflammatory factors in mise colon tissue was measured by ELISA,the expression of ZO-1,E-cadherin and Occludin was assessed by immunohistochemistry and RT-PCR,and changes in the diversity and community structure of intestinal bacteria were assessed by 16 s RNA sequencing.The following main results of the experiment were obtained.Firstly,The results showed that during the modeling period,the body weight of mice in the control group kept showing an increasing trend,while the other three groups showed an increasing and then decreasing trend,in which the body weight of mice in the probiotic R1 fermented camel milk group and camel milk group decreased more slowly after the intervention than that in the model group.After successful modeling,the colon length of the probiotic R1 fermented camel milk group was significantly greater than that of the model group(P<0.05),and the colon histopathology score was significantly lower than that of the model group(P<0.05).Secondly,the levels of TNF-α,IFN-γ,IL-1β and IL-6 in colonic tissues showed all a decreasing trend after intervention with probiotic agent R1 fermented camel milk and camel milk group compared with DSS,while the levels of IL-4 and IL-10 increased,and the relative expression of three tight junction protein m RNAs,ZO-1,E-cadherin and Occludin,increased,but they were all below control group.Thirdly,the analysis of intestinal microbial diversity showed that Observed species,Chao1,Shannon,and PD＿whole＿tree in alpha diversity index were elevated,and the the diversity and richness of intestinal bacteria in fermented camel milk and camel milk group were higher than those in control group and the model group in the PCo A.The relative abundance of Firmicutes increased and the relative abundance of Bacteroidetes,Verrucomicrobiae,and Actinobacteria decreased after probiotic R1 fermentation of camel milk intervention.In addition,probiotic R1 fermentation of camel milk increased beneficial bacteria(Ruminococcaceae UCG-014,Prevotellaceae UCG-001,and Muribaculum)and decreased harmful bacteria(Bacteroides and Oscillibacter)in the intestine.Fourthly,correlation analysis showed that Lachnospiraceae NK4A136 group,Parabacteroides,and Alloprevotella were positively correlated with colon length,IL-10,relative expression of tight junction protein gene,and immunohistochemical score,while Bacteroides,Parabacteroides,Oscillibacter,and Akkermansia were negatively correlated with colon length,IL-10,relative expression of tight junction protein genes,and immunohistochemical scores.In conclusion,the probiotic agent R1 fermented camel milk prevented the development and progression of ulcerative colitis by upregulating the expression of ZO-1,E-cadherin and Occludin,inhibiting the expression of inflammatory response factors,promoting the expression of anti-inflammatory factors and improving the multiplicity and community structure of the intestinal flora.