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Abstract: TH-OR56

Phascolarctobacterium-Producing Propionate and Acute Rejection Among Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Cho, Hyunjeong, Chungbuk National University Hospital, Cheongju, Korea (the Republic of)
  • Kim, Ji Eun, Korea University Guro Hospital, Seoul, Korea (the Republic of)
  • Lee, Jangwook, Dongguk University Ilsan Hospital, Goyang, Gyeonggi-do, Korea (the Republic of)
  • Kim, Yong Chul, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Park, Ji In, Kangwon National University Hospital, Chuncheon, Kangwon, Korea (the Republic of)
  • Lee, Jung Pyo, Seoul National University Hospital, Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Yon Su, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Lee, Hajeong, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
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. Recent studies have shown that gut microbiota regulates host immune response, although the association between gut microbiota and AR in kidney transplant (KT) recipients is poorly understood. Here, we aimed to evaluate the gut microbiota and its metabolites 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 12 months (n=33). Metagenomic DNA from feces was sequenced using by Illumina MiSeq system. Stool metabolites were measured by a 1H nuclear magnetic resonance spectroscopy. We obtained various clinical factors including biopsy-proven AR within 1 year after KT.

Results

Within the 1st year of the transplantation, 33 (34%) patients developed AR. Bacterial richness (observed ASVs) and diversity of the microbial communities (Shannon diversity index) were lower in the AR group than in the non-rejection group (PFDR=0.07, PFDR=0.02, Wilcoxon rank-sum test with FDR). In ALDEx2 analysis, at the genus level, the Escherichia-Shigella had significantly increased abundance in the AR group compared to that in the non-rejection group (PFDR < 0.25), while the Phascolarctobacterium was significantly decreased (PFDR < 0.25) in the AR group compared to in the non-rejection group. In ROC analysis, two bacteria adding clinical values significantly predict AR (AUC: 0.897). In LEFSe analysis based on the PICRUSt2 results, we found 83 differentially abundant metaCyc pathways in the AR group than in the non-rejection group (LDA score > 2.0 and P < 0.05). In particular, pathways of homolactic fermentation and mixed acid fermentation were enriched in the AR group. And finally, fecal propionate, a key metabolite of short-chain fatty acid was 12% lower in the AR group than in the non-rejection group (p=0.05).

Conclusion

In this study, we found that pre-transplant decreased relative abundance of Phascolarctobacterium was associated with AR after KT. In addition, its fecal propionic acid which was known to be produced by Phascolarctobacterium was decreased in the AR group.