Changes Of Intestinal Flora In Chronic Nephropathy And Its Mechanism In Disease Progression

Objective:To investigate the changes of intestinal flora and differential bacteria in patients with chronic kidney disease,and to evaluate the diagnostic value of differential bacteria for CKD and its correlation with renal function.To determine the changes of inflammatory factors in patients with chronic kidney disease in noninfectious state,and analyze the correlation between different bacteria and inflammatory factors in CKD patients,so as to provide a new clue for the pathogenesis of CKD and a new target for the treatment of CKD.Methods:Fecal specimens were collected from 56 patients with CKD and 38 healthy controls in the Nephrology Department and Medical Examination Center of Shanxi People's Hospital between August 2017 and January 2018.High-throughput sequencing analysis of 16 S rDNA V3-V4 hypervariable regions was performed for intestinal flora.Intestinal flora in CKD patients and healthy subjects were analyzed for alpha,beta diversity,species composition analysis,and differential species analysis.The diagnostic value of the presence of specific intestinal flora for CKD was analyzed using a receiver operating characteristic curve(ROC).Pearson's correlation analysis was used to analyze the correlation between the presence of specific genera and the estimated glomerular filtration rate(eGFR).We measured the changes of inflammatory factors in CKD patients with quantitative cytokine array method,and analyzed whether the changes of intestinal flora were related to the production of CKD related inflammatory factors.Results:The alpha and beta diversity in the CKD group was different from that in the control group(P < 0.05).At the phylum level,Verrucomicrobia were significantly less abundant in the CKD group than in the control group(0.70%vs3.09%)(P?0.001).The abundance of Actinobacteria was significantly greater in the CKD group than in the control group(1.48%vs 1.14%)(P=0.036).At the genus level,the abundance of Akkermansia(0.96%vs3.90%),Parasutterella(0.47%vs0.93%),and Lactobacillus(0.07% vs.0.48%)in the CKD group was significantly less than those in the control group(all P ?0.01).The abundance of Alloprevotella(0.41%vs0.04%)and Clostridium IV(0.6%vs.0.1%)was significantly greater than those in the control group(all P?0.05).The diagnostic value of CRF for the area under the ROC curve(AUC)for Akkermansia was 0.753,and that for Lactobacillus diagnostic value of CRF was 0.792..The combined AUC diagnostic value of CKD for detection of Akkermansia and Lactobacillus was 0.830,with high disease prediction value.Lactobacillus abundance was positively correlated with eGFR(r=0.29,P=0.029).The indexes of IL-4,IL-6 and IL-10 in CKD group were significantly higher than those in healthy control group(P < 0.05).The change of intestinal flora is related to the production of inflammatory factors.Akkermansia was negatively correlated with IL-10 production(P < 0.01),The other nine genera,including allobaculum,alloprevotella,enterrhabdus,eucharacterium,Helicobacter,Lactobacillus,olsenella,paraprevotella and pyromidobacter,were negatively correlated with IL-10 and IL-4(P < 0.05).Only holdemania was positively correlated with IL-6(P < 0.05).Conclusion:The diversity and structure of intestinal flora are altered in patients with CKD.The abundance of Akkermansia and Lactobacillus has diagnostic value for CKD.The abundance of Lactobacillus is positively correlated with eGFR.The inflammatory factors of CKD patients were significantly increased and akkermansia was negatively correlated with the production of IL-10.Studies have shown that changing intestinal flora may be a promising potential therapeutic strategy to reduce CKD progression and systemic inflammation.