Targeted Metabolomics Study Of Serum Bile Acid Profile In Patients With End-stage Renal Disease Undergoing Hemodialysis

BackgroundBile acids,as important metabolites of intestinal microbiota,have been found to act as endogenous signaling molecules conjugated to bile acid receptors so as to play a role in lipid metabolism,electrolyte transport,blood glucose regulation,and immune regulation.Chronic kidney disease is characterized by metabolic disorders in terms of protein,fat,sugar,vitamins,water,electrolytes and acid-base.However,whether metabolism of bile acids is involved in the above metabolic disorders is currently unclear.Therefore,we performed a quantitative analysis of bile acid profile in patients with end-stage renal disease(ESRD).MethodsA targeted metabolomics approach based on ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to explore the changes in serum bile acid metabolism of ESRD patients(n=77)and healthy controls(HCs)(n=30).Univariate and multivariate statistical analyses were performed to screen the differential bile acids between the two groups.The diagnostic efficacy of differential metabolites was evaluated by receiver operating characteristic curve(ROC).Subgroup analysis of bile acid profiles in 30 ESRD survival groups,17 ESRD death groups and healthy controls using one-way ANOVA and post hoc multiple testing.Results1.A total of 31 types of targeted serum bile acids were analyzed,26 of which were positively detected.2.The differences in bile acid profile between the ESRD group and the HCs group was detected by Mann-Whitney U test.The proportions of unconjugated bile acids cholic acid(CA),chenodeoxycholic acid(CDCA),deoxycholic acid(DCA),hyodeoxycholic acid(HDCA),ursodeoxycholic acid(UDCA),α-muricholic acid and ω-muricholic acid(α+ωMCA),γ-murocholic acid(γMCA),7-ketolithocholic acid(7KLCA),12-ketolithocholic acid(12KLCA),and 6,7-diketolithocholic acid(6,7-diketoLCA)all decreased in the ESRD group compared with the HC group(p<0.05).the proportions of conjugated bile acids glycocholic acid(GCA),glycochenodeoxycholic acid(GCDCA),taurocholic acid(TCA),taurochenodeoxycholic acid(TCDCA),taurohyocholic acid(THCA),tauro α-muricholic acid(TαMCA),and tauroursodeoxycholic acid(TUDCA)increased,with significant differences(all p<0.05)between the two groups.3.OPLS-DA and ROC curve screened out six different bile acids of GCDCA,TCDCA,GCA,CDCA,DCA and CA as typical differential metabolites for distinguishing between ESRD and HC.4.subgroup analysis showed that the proportion of TCA,TCDCA,THCA,and TαMCA in the control group,ESRD survival group,and ESRD death group increased successively with statistically significant differences(p <0.1).ConclusionThe serum bile acid profile of ESRD patients is significantly different from that of HCs,which may be associated with intestinal microbiota changes in ESRD patients.The altered serum bile acid profile may participate in the occurrence of dyslipidemia and its complications through signaling pathways.