Kidney Week

Abstract: FR-PO1001

Gut Microbiome Alterations Precede Graft Rejection in Kidney Transplantation Patients

Session Information

• Transplantation: Basic
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2101 Transplantation: Basic

Authors

• Holle, Johannes, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany

Johannes Holle, DrMed

• Reitmeir, Rosa Petra, Max Delbruck Centrum fur Molekulare Medizin Experimental and Clinical Research Center, Berlin, Berlin, Germany

Rosa Petra Reitmeir

• Behrens, Felix, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany

Felix Behrens, MD

• Schindler, Daniela, Deutsches Zentrum fur Infektionsforschung eV Standort Munchen, Munchen, Bayern, Germany

Daniela Schindler

• Gerhard, Markus, Deutsches Zentrum fur Infektionsforschung eV Standort Munchen, Munchen, Bayern, Germany

Markus Gerhard

• Oh, Jun, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Jun Oh, MD

• Löber, Ulrike, Max Delbruck Centrum fur Molekulare Medizin Experimental and Clinical Research Center, Berlin, Berlin, Germany

Ulrike Löber, MSc, PhD

• Wilck, Nicola, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany

Nicola Wilck, MD

• Bartolomaeus, Hendrik, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany

Hendrik Bartolomaeus, MD

Background

Kidney transplantation (KT) is the optimal treatment for end-stage kidney disease, with graft survival critically affected by the recipient's immune response. The role of the gut microbiome in modulating this immune response remains underexplored. Our study investigates how microbiome alterations might associate with allograft rejection.

Methods

We analyzed existing biomaterials of a multicenter prospective study involving 217 KT recipients and 28 kidney donors from the German Center for Infection Research. Changes in the gut microbiome were analyzed using 16S rRNA gene amplicon sequencing and functional predictions (PICRUSt2) and quantitative PCRs for the production potential of propionate and butyrate. Propensity score matching was utilized to compare patients who experienced graft rejection with those who did not.

Results

The gut microbiome showed gradual recovery post-KT, marked by an increase of Shannon diversity and SCFA-producing bacterial taxa. However, prior to graft rejection, significant alterations were noted in microbiome composition, characterized by a decrease in microbial diversity and SCFA-producing taxa. Post-rejection analysis revealed normalization of these microbiome features. Functional analysis highlighted a decreased potential for SCFA production in patients prior to rejection. Comparison to published associated microbiome signatures from chronic kidney disease (CKD) patients demonstrated a partial overlap of the microbiome alterations preceding graft rejection with the alterations typically found in CKD.

Conclusion

Our findings suggest that alterations in the gut microbiome composition and function may precede and influence KT rejection, suggesting potential for use as biomarker and early therapeutic microbiome-targeting interventions to improve transplant outcomes.