Gut microbiome alterations precede graft rejection in kidney transplantation patients
Kidney transplantation (KT) is the best 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 be associated with allograft rejection by analyzing the gut microbiome using 16S rRNA gene amplicon sequencing of a multicenter prospective study involving 562 samples from 245 individuals of whom 217 received KT. Overall, gut microbiome composition showed gradual recovery post-KT, mirroring chronic kidney disease (CKD)-to-health transition as indicated by an increase in Shannon diversity. Prior to graft rejection, we observed a decrease in microbial diversity and short-chain fatty acid-producing taxa. Functional analysis highlighted a decreased potential for short-chain fatty acid production in patients preceding the rejection event, validated by quantitative PCR for the production potential of propionate and butyrate. Postrejection analysis revealed normalization of these microbiome features. Comparison to published microbiome signatures from CKD patients demonstrated a partial overlap of the microbiome alterations preceding graft rejection with the alterations typically found in CKD. Our findings suggest that alterations in gut microbiome composition and function may precede and influence KT rejection, suggesting potential implications as biomarkers or for early therapeutic microbiome-targeting interventions.
Authors
- Nicola Wilck (ORCID: https://orcid.org/0000-0003-3189-5364)
- Michael Neuenhahn (ORCID: https://orcid.org/0000-0003-0400-2743)
- Jun Oh (ORCID: https://orcid.org/0000-0003-1846-675X)
- Markus Gerhard (ORCID: https://orcid.org/0000-0001-9110-3950)
- Uwe Heemann (ORCID: https://orcid.org/0000-0002-3886-2517)
- Harithaa Anandakumar (ORCID: https://orcid.org/0009-0000-3326-5126)
- Sofia Kirke Forslund (ORCID: https://orcid.org/0000-0003-4285-6993)
- Dharmesh Singh (ORCID: https://orcid.org/0000-0001-8318-3954)
- Victoria McParland (ORCID: https://orcid.org/0000-0003-0731-3272)
- Hendrik Bartolomaeus (ORCID: https://orcid.org/0000-0003-4288-3828)
- Ulrike Löber (ORCID: https://orcid.org/0000-0001-7468-9531)
- Daniela Schindler
- Steffen Hartleif (ORCID: https://orcid.org/0000-0002-2608-5087)
- Claudia Sommerer (ORCID: https://orcid.org/0000-0001-5080-0979)
- Johannes Benjamin Holle (ORCID: https://orcid.org/0000-0001-8032-4096)
- Joachim Andrassy (ORCID: https://orcid.org/0000-0001-8303-3913)
- Nele Kanzelmeyer (ORCID: https://orcid.org/0000-0002-4865-4906)
- Felix Behrens (ORCID: https://orcid.org/0000-0002-6841-4192)
- Rosa Reitmeir
- Olena Potapenko
Institutions
- Helmholtz Association of German Research Centres (DE)
- Universität Hamburg (DE)
- Max Delbrück Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Medizinische Hochschule Hannover (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- German Center for Infection Research (DE)
- University Children's Hospital Tübingen (DE)
Publication Details
- Journal
- American Journal of Transplantation
- Published
- 2025-02-18
- DOI
- https://doi.org/10.1016/j.ajt.2025.02.010
- Citations
- 8
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 6.45
Funders
- Deutsches Zentrum für Infektionsforschung
- Corona-Stiftung
- European Commission
- Bundesministerium für Bildung und Forschung
- Else Kröner-Fresenius-Stiftung
- Horizon 2020 Framework Programme
- European Research Council
- HORIZON EUROPE European Research Council