Korean J Transplant.  2022 Nov;36(Supple 1):S262. 10.4285/ATW2022.F-4039.

Phascolarctobacterium-producing propionate and acute rejection of kidney transplant recipients

Affiliations
  • 1Division of Nephrology, Department of Internal Medicine, Chungbuk National University Hospital, Cheonju, Korea
  • 2Division of Nephrology, Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea
  • 3Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
  • 4Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
  • 5Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
  • 6Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

Abstract

Background
Acute rejection (AR) is associated with worse long-term allograft survival. Therefore, identifying and regulating the potential risk factors of AR is very important. Growing evidence has shown that gut microbiota regulates host immune response. Here, we aimed to evaluate the gut microbiota and its metabolites that could predict AR after kidney transplantation (KT).
Methods
We prospectively collected 98 KT recipients stool samples at pretransplant (n=97), posttransplant 3 months (n=66), and posttransplant 12 months (n=33). Metagenomic DNA was isolated from feces and was sequenced using by Illumina MiSeq system. Stool metabolites were measured by a 1 H nuclear magnetic resonance spectroscopy. We obtained various clinical fac-tors including biopsy-proven AR within 1 year after KT.
Results
Within the 1st year of the transplantation, 33 patients (34%) developed AR. Bacterial richness (observed amplicon se-quence variants) and diversity of the microbial communities (Shannon index) were lower in the AR group than in the nonrejec-tion group (Wilcoxon rank-sum test with false discovery rate [FDR]; P FDR =0.07 and P FDR =0.02, respectively;). The genus Escherichia-Shigella was significantly increased (P FDR <0.25), while the Phascolarctobacterium was decreased (P FDR <0.25) in the AR group compared to the nonrejection group. In linear discriminant analysis (LDA) effect size (LEFSe) analysis, we found 83 differentially abundant MetaCyc pathways in the AR group than in the nonrejection group (LDA score, >2.0; P<0.05). Pathways of homolactic fermentation and mixed acid fermentation were enriched in the AR group. Fecal propionate, a key metabolite of short-chain fatty acid and lactate was lower in the AR group than in the nonrejection group (P=0.05 and P=0.02, respectively). In the comparison of two receiver operating characteristic (ROC) curves, two bacteria and two metabolites adding clinical val-ues provide a better prediction of AR (area under the ROC curve [AUC], 0.958) than only clinical values (AUC, 0.849; P=0.006).
Conclusions
In this study, we found that pretransplant decreased relative abundance of Phascolarctobacterium was associated with AR after KT. In addition, fecal propionic acid which was known to be produced by Phascolarctobacterium was decreased in the AR group.

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