Pre-transplant Ratio of Firmicutes/Bacteroidetes of Gut Microbiota as a Potential Biomarker of Allograft Rejection in Renal Transplant Recipients

Abstract

The advent of technologies has made allogenic transplantation a potential curative therapy for end-stage renal diseases, but the episodes of rejection still remain as one of the challenges in the post-transplant scenario. In the recent years, several human and animal studies have elucidated that gut microbial dysbiosis is closely linked with allogenic transplantation and post-transplant complications. But most of the studies focused on the use of high through-put sequencing technologies to analyze gut microbiota despite of its high cost, analysis and time constraints. Hence, in this work we aimed to study the impact of the two dominant gut phyla Firmicutes and Bacteroidetes on 38 renal transplant recipients, before and after transplantation and to find its association with allograft rejection. Significant changes (p<0.01) were observed in the relative abundances of the phyla Firmicutes and Bacteroidetes at pre- and post-transplant period. We have also found that the recipients who had an increase in Firmicutes/Bacteroidetes (F/B) ratio before transplant were highly prone to rejection in the first-year post-transplant. The Receiver Operating Characteristic (ROC) curve analysis has shown that the ratio of F/B were able to discriminate between rejection and non-rejection cases with an Area under the ROC Curve (AUC) of 0.91. Additionally, we observed that the ratio of F/B have reduced during the time of rejection postulating that gut microbial dysbiosis has more association with rejection. Thus, the assessment of F/B ratio using qPCR would be of a more practical approach for diagnosis and monitoring of graft function in a cost-effective and timely manner.