Urine microbiota profiling in renal transplant recipients during acute allograft inflammation

Purpose: The urobiome of renal transplant recipients is poorly defined. Our goal was to characterize the urobiome in steady post-transplant states and during cell-mediated allograft rejection.Methods: 42 patients consented to have urine (n=86) collected via mid-stream clean catch technique prior to transplant (n=22), at time of cell-mediated rejection (n=10; within 1 month of transplant), 1-month post-transplant (n=16) and 3-months post-transplant (n=38). Samples were processed and stored at -80C until 16S rRNA sequencing and bioanalysis. Alpha (species richness) and beta diversity (microbiome composition) analysis between rejector and non-rejector groups was performed.Results: 5 groups were formed: 1) Rejectors (n=10 pts; mean age 48.7+/-12.4 yrs); 2) Women <50 yrs (n=8 pts); 3) Women >50 yrs (n=8 pts); 4) Men <50 yrs (n=8 pts); 5) Men >50 yrs (n=8 pts).Urine Ssamples compared to non-transplant control urine differedwere unique to negative controls by beta (p=<0.003), but not alpha diversity (p=0.61). All groups displayed a general loss of taxa post-transplant, with rejectors gaining Corynebacterium and non-rejectors gaining Bifidobacterium and Peptoniphilus. Within individuals, the post-transplant microbiome was comprised of 75% unique taxa compared to pre-transplant urine (p<0.001). There was a clear, independent association of microbiome composition with sex (beta diversity; p=<0.0021), but not with age.Conclusions: Data suggests that renal transplantation has a strong impact on an individuals urobiome composition. It is possible that the urobiome from the donor is transplanted along with the kidney, which could explain the stark differences seen (75% turnover). However, thefactors that differentiate rejectors and non-rejectors are unknown based on current data.