Correlation Between Gut Microbiota And Its Metabolites And Diabetes Mellitus After Renal Transplantation

BACKGROUND: Posttransplantation diabetes mellitus(PTDM)is a common complication with high incidence after renal transplantation,which can cause adverse effects on the quality of life of the recipient and the long-term survival of the graft,but its related occurrence and development mechanisms are still unclear.RESEARCH PURSOSES: Under the background of long-term immunosuppressive used by renal transplant recipients(RTRs),by exploring the the characteristics of PTDMrelated gut microbiota and metabolites,to provide new ideas for studying the occurrence and development mechanism of PTDM,and then provides evidence for early screening and prevention of PTDM.METHODS: A total of 100 RTRs were enrolled in this study,and they were divided into 3 groups: control group(normal glucose tolerance),impaired fasting glucose(IFG)group and PTDM group.Two detections were performed on the collected stool samples of recipients: one was to sequence the V4-5 region of the 16 S rRNA gene to obtain the classification and abundance information of the gut microbiota;the other was to perform non-targeting metabolome detection based on liquid chromatography-mass spectrometry technology to obtain the functional characteristics and metabolic mode of the stool samples.At the same time,the information of environmental exposures is obtained through questionnaires,which is used to assess the correlation between environmental factors and PTDM.RESULTS: 36% of RTRs had abnormal glucose metabolism,and 17% of RTRs were diagnosed with PTDM.Significant difference was identified in beta diversity based on Unweighted Unifrac,but not in alpha diversity of gut microbiota between the control,IFG and PTDM groups.12 distinguishing components at different taxon levels analyzed by LEFSe,including 2 species enriched in PTDM group and 10 species enriched in control group(LDA?score >?2.5).The consumption of coarse grains,dietary supplements and alcoholic beverages were key factors affecting the gut microbiota of RTRs,and the consumption of coarse grains was significantly negatively correlated with fasting plasma glucose(FPG)(Spearman correlation coefficient =-0.2397,P-value <0.05).Fecal metabolome analysis revealed the different metabolic patterns of among the Control/IFG/PTDM groups,which can significantly distinguish the Control/IFG/PTDM groups based on Partial Least Squares Discriminant Analysis.Based on GABA,the ROC curves were constructed for two pairs of groups(the PTDM and Control groups,the IFG and Control groups),whose AUCs were 0.7621 and 0.8125,respectively.A total of 137metabolites(9 up-regulated and 127 down-regulated)were significantly differentially expressed between the PTDM and control groups,of which hydroquinone was significantly positively correlated with FPG(Spearman correlation coefficient=0.422,Pvalue<0.001),and the expression of GABA and pregnenolone was significantly negatively correlated with FPG.Tyrosine metabolism was the only KEGG metabolic pathway significantly enriched by the differential metabolites of two pairs of groups(PTDM vs control,and IFG vs control).COUCLUSION: This study preliminarily analyzed the characteristics of the gut microbiota and metabolites associated with PTDM in RTRs,and provided a new insight for the further study of the mechanism of PTDM.