Studay Of Astragalus And Astragalus Polysaccharides Modulate Gut Microbiota And Metabolism In CKD Rats

ObjectiveCKD has always been one of the diseases that seriously affect people’s life quality.Due to the particularity of CKD,it will gradually develop into a series of secondary nephropathy and kidney failure in the later stage,so far the pathogenesis of CKD has not been deeply studied,so it is very important to explore the treatment target of chronic nephritis.Astragalus membranaceus is commonly used in traditional Chinese medicine which protect kidney by invigorating spleen.Although some studies have shown that Astragalus membranaceus can treat kidney by immunomodulation,promoting protein synthesis,anticoagulation,promoting fibrinolysis and lowering fat.However,researches on nephropathy treatment based on TCM theory is minimal.Here,we found that theory of"gut-renal axis" fits the idea of "tonifying spleen and treating kidney " perfectly.Therefore,we are trying to explains the effect of Astragalus and Astragalus Polysaccharides based on intestinal microenvironment and renal excretion.Methods1.Establishment of CKD model and therapeutic evaluation of Astragalus and Astragalus polysaccharidesA model of rats with CKD was established by C-BSA tail intravenous injection.HE staining,24h UP,BUN,Scr and inflammatory factors were observed to evaluate model and drug efficacy2.Intestinal flora analysisFecal samples were measured using 16 S rRNA sequencing technology via Illumina Mideq platform for data analysis.The flora was clustered by OTU analysis,α diversity and β diversity were observed to estimate the differences in and between groups.Difference test and LEfSe were used to find marker metabolite functional flora.Meanwhile,PICRUSt were apply to forecast flora function.3.Metabonomics analysisWe used 600 MHz 1H NMR for non-target metabolomics assays to determine urine,fecal metabolites.multivariate statistical analysis were used to evaluate metabolite profiles.What’s more,visualize metabolic pathways and differential metabolites through metaboanalyst were applied to find differential metabolites and pathways,trying to analyse marker metabolites and evaluate their physiological significance.Results1.Model was successfully established and Astragalus and Astragalus polysaccharides had therapeutic effects on CKD to some extent.Compared with the control group,C-BSA did heavier harm to colon and kidney in model group,and the contents of 24h UP,Scr,BUN and inflammatory factor（TNF-α,IL-6,IL-17and IL-23）were increased.After administration,Astragalus and Astragalus polysaccharides could alleviate damage,and 24 UP,Scr,BUN and inflammatory factor（TNF-α,IL-6,IL-17and IL-23）contents were also reduced.2.Chronic nephritis and intervention of Astragalus and Astragalus Polysaccharide affect intestinal flora structureCompared with the control group,the model group showed decrease of Rumen cocci,but increase of Erysipelotrichaceae_UCG₀03;after administration,Astragalus membranaceus could increase the abundance of the beneficial bacteria,such as Alloprevotella,Weissella,Papillibacter;and Astragalus polysaccharides could increase the abundance of beneficial bacteria such as Ruminococcaceae_UCG₀04,norank_fLachnospiraceae and Desulfovibrio.3.CKD and intervention of Astragalus and Astragalus Polysaccharide affect metabolism of intestinal flora and organism.The content of creatinine,hippurate,glutamine,arginine,,p-cresol sulfate and phosphatidylcholine in urine decreased in the model group compared with the control group and other two medication administration groups,Astragal polysaccharide can also increase SCFAs to protect colon and kidney.but the content of methionine and short chain fatty acids increased in feces.ConclusionThrough the above research,it is found that kidney injury causes intestinal microenvironment disorder,causes metabolic changes of body and intestinal flora,and increases endotoxin production.Astragalus and Astragalus polysaccharide administration intervention to correct intestinal flora disorders,reduce endotoxin damage.According to the study of intestinal flora and metabolites,this experiment fully demonstrates the connotation of Astragalus membranaceus "tonifying spleen and treating kidney",organically combines TCM syndrome differentiation and treatment with modern theory,which provides a new way for the treatment of chronic nephritis and a new basis for TCM treatment theory...