Mechanism Of Changyanning In Alleviating Gut Microbial Dysbiosis And Treating With Inflammatory Bowel Disease

Objective Inflammatory bowel disease(IBD),represented by Crohn disease and ulcerative colitis,which are auto-immune induced by genes,environment,and immune response.Intestinal flora imbalance reported be one of the causes of IBD.Restoring the disordered intestinal flora has become a research hot spot in the prevention and treatment of IBD.Changyanning is mainly made up of Euphorbia humifusa Willd,Herba hedyotids chrysotrichae,Cinnamomum camphora,Elsholtzia ciliata,maple leaves,etc.Clinical studies have shown that Changyanning has a significant effect on ulcerative colitis alone or in combination,but the treatment mechanism is not clear.In this study,animal model of IBD was established to explore the treatment mechanism of Changyanning for IBD and its effect on the intestinal flora impact.Method Male C57BL/6 SPF mice were given 4% dextran sodium sulfate(DSS)to drink freely for 7 days to establish an experimental colitis model;SPF healthy SD male rats underwent rectal perfusion with 2,4,6-trinitrate Benzene sulfonic acid(TNBS,60 mg/kg)under anesthesia to set up IBD model.After the two models were established,different doses of Changyanning tablets and granules,sulfasalazine(SASP)were administered by gavage for 7 days.Evaluate the alleviating effects of the above drugs on IBD by evaluating mouse/rat weight,survival rate,disease activity index(DAI),colon length,histopathological section,and levels of colon tissue inflammation factors.The Illumina HiSeq sequencing platform was used to investigate the regulation of the intestinal flora of inflammatory bowel mice/rats by drugs based on the bacterial 16 S r RNA gene V3-V4 variable region,and the dominant bacteria in each drug intervention group were identified.Results1.DSS-induced IBD mouse model loss weight,DAI score,pathological score significantly increased(P <0.0001),Changyanning tablets and granules can alleviate weight loss,restore colon length,and protect colon tissue structure,decrease the DAI and pathological scores of mice.Changyanning granules have better effect.Changyanning tablets and granules stimulate the growth of Verrucomicrobia,Firmicutes,Lactobacillus,Akkermansia,Porphyromonadaceae_unclassified,and inhibit the growth of Proteobacteria,Deferribacteres,Escherichia,and Bacteroides to regulate the intestinal flora and promote the restoration of homeostasis.2.The weight gain rate of IBD rat model induced by TNBS was significantly reduced,the DAI and HS were significantly increased(P <0.0001),the symptoms of colon ulcer and necrosis were severe;Changyanning tablets and granules could improve the intestine of UC rats obstruction,reduced ulcer area,and reduced pathological scores,but did not show significant improvement in weight and colon length.After the treatment of Changyanning tablets and granules,the intestinal flora diversity has recovered,and by increasing the relative abundance of bacteria such as Firmicutes,Verrucomicrobia,Lachnospiraceae_NK4A136,Akkermansia,Lactobacillus,and reducing Bacteroidetes abundance to regulate the TNBS-induced rat intestine disorders of flora.Conclusion In summary,Changyanning improved the quality of life of IBD model animals significantly,alleviate the intestinal inflammatory response of IBD,reduce colon edema,ulcers and necrosis,reduce infiltration of inflammatory cells in the diseased colon mucosa,and promote mucosal healing.It can also increase the intestinal flora diversity of IBD model animals,and adjust the composition of intestinal flora to restore the flora disorder.This article also provides experimental evidence for the application of Changyanning in the treatment of IBD,which is of great significance for its further promotion application.