Microbial and metabolic features in renal transplant recipients with posttransplantation diabetes mellitus

Context: As a common complication after renal transplantation, posttransplantation diabetes mellitus (PTDM) is associated with the decreased quality of life of the renal transplant recipients (RTRs), but the lack of a complete understanding of the mechanisms of PTDM genesis thwarts its treatment and prevention.

Objective: To investigate the characteristics and association of gut microbiota and fecal metabolites in RTRs with PTDM.

Methods: Fecal samples were collected from RTRs, and its composition of gut microbiota and fecal metabolites were detected by using 16S rRNA gene V4-5 region sequencing and liquid chromatography-mass spectrometry, respectively. The information of environmental exposures is obtained through questionnaires.

Results: 17% of RTRs were diagnosed with PTDM. Fecal metabolome analysis revealed the unique distribution characteristics of metabolites of RTRs with PTDM, and could distinguish RTRs with impaired fasting glucose(IFG)/PTDM from RTRs with normal glucose tolerance. Specific metabolites (GABA, pregnenolone, hydroquinone, etc.) differentially expressed in RTRs with PTDM were correlated with fasting plasma glucose(FPG). Significant difference was identified in composition and abundance, but not in richness of gut microbiota in RTRs with PTDM. 12 distinguishing components of gut microbiota were found in RTRs with PTDM. The consumption of coarse grains was correlated with the composition of gut microbiota, and negatively correlated with FPG.

Conclusion: Our study revealed the features of the gut microbiota and fecal metabolites in RTRs with PTDM, and identified a new set of key PTDM-related metabolites and bacteria, which can provide a new direction for further studies aiming to understand the occurrence of PTDM.