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Study examines the gut microbiome of transplanted kidney recipients from the DZIF transplant cohort and establishes a link between microbial changes in the gut microbiome and transplant rejection and graft dysfunction. The results offer a possible starting point for detecting the risk of rejection at an early stage.
Kidneys are the most transplanted organ in Germany. According to the German Organ Transplantation Foundation, a total of 1,514 kidneys were transplanted after post-mortem organ donation in 2023, out of a total of 2,986 transplanted organs. For patients with advanced kidney failure, a kidney transplant remains the best treatment option. The demand is correspondingly high: in 2023, 6,513 patients were on the waiting list for a kidney transplant. A serious risk for patients who have already received a transplant is rejection of the transplant. This is a defensive reaction of the body against the foreign tissue, which can lead to a complete loss of organ function in an emergency. Why transplants are sometimes rejected and sometimes not depends largely on immune mechanisms. The causes are complex and often poorly understood. To help answer this question, researchers from Charité - Universitätsmedizin Berlin, the Max Delbrück Center for Molecular Medicine and the German Center for Infection Research (DZIF) have analyzed the changes in the composition and function of the gut microbiome of kidney transplant patients who were included in the DZIF transplant cohort. They discovered an altered signature in the gut microbiome that preceded transplant rejection. This study, published in the American Journal of Transplantation, offers a possible starting point for recognizing the risk of rejection at an early stage.
Our gut is home to countless microorganisms that play an important role in how our immune system works. This is known as the microbiome. The majority of these, over 90 %, are bacteria. These bacteria and the substances they produce communicate with our body - especially with the cells that protect us from disease. They therefore help to control and strengthen our immune system, which is important for both healthy and sick people. In patients with chronic kidney disease, the composition of the gut microbiome is severely altered, resulting in lower concentrations of anti-inflammatory short-chain fatty acids (SCFA) and increased concentrations of pro-inflammatory metabolites from the microbiome.
In their study, researchers led by first authors Johannes Holle and Rosa Reitmeir from Nicola Wilck's research group at the Experimental and Clinical Research Center, a joint institution of the Charité and the Max Delbrück Center in Berlin, analyzed the changes in the composition and function of the gut microbiome of patients after kidney transplantation. They found changes in the gut microbiome that were already detectable before the transplant rejection reaction. All patients analyzed in this study were part of the prospective cohort study of the DZIF, which was conducted at five German transplant centers in university hospitals in Heidelberg, Hanover, Tübingen and in Munich at the Technical University and the Ludwig-Maximilians-University. Together, these centers cover over 20 % of organ transplants in Germany and provide a representative picture of the course after kidney transplantation.
The analysis of a total of 562 stool samples, grouped by healthy kidney donors, patients before kidney transplantation, 0-3 months after kidney transplantation, 3-12 months, 12-24 months and over 24 months after kidney transplantation, shows a dynamic regeneration of the microbiome over time after kidney transplantation, with the microbiome returning to its natural and healthy state over.
"Since we observed this dynamic change, we wanted to understand whether and how transplant rejection influences this process," explains Johannes Holle. "And vice versa, how microbiome changes can affect the immunity and rejection of transplants," adds Rosa Reitmeir. The researchers found that patients who had experienced transplant rejection had an altered composition of the gut microbiome even before the clinically conspicuous and biopsy-proven rejection reaction.
It was noticeable that in patients who showed a rejection reaction, bacteria that typically occur in patients with advanced kidney failure, such as Fusobacterium and disease-associated genera such as Streptococcus, increased again. This was not the case in the other group studied, the "non-rejection group". Overall, the analyses showed that the production potential of short-chain fatty acids in the stool is reduced before kidney rejection. This is indicated by the reduced frequency of bacterial enzymes from which short-chain fatty acids are produced before rejection.
The previously observed dynamic regeneration of the microbiome after kidney transplantation may be significantly disturbed in the case of transplant rejection: prior to rejection, profound changes in the composition of the microbiome occur, characterized by reduced diversity and a low number of SCFA-producing bacterial populations. "Our results suggest that the microbiome plays an important role in how the immune system reacts after a kidney transplant. This observation can help to identify the risk of transplant rejection at an early stage or perhaps influence it therapeutically," summarize Holle and Reitmeir.
Dr. Daniela Schindler
DZIF Transplant Cohort
daniela.schindler@tum.de
https://www.dzif.de/en/working-group/transplant-cohort
Holle J, Reitmeir R, Behrens F, Singh D, Schindler D, Potapenko O, McParland V, Anandakumar H, Kanzelmeyer N, Sommerer C, Hartleif S, Andrassy J, Heemann U, Neuenhahn M, Forslund-Startceva SK, Gerhard M, Oh J, Wilck N, Löber U, Bartolomaeus H. Gut microbiome alterations precede graft rejection in kidney transplantation patients. Am J Transplant. 2025 Feb 18:S1600-6135(25)00093-0. doi: 10.1016/j.ajt.2025.02.010. Epub ahead of print. PMID: 39978595. https://doi.org/10.1016/j.ajt.2025.02.010
https://www.dzif.de/en/gut-microbiome-predictive-factor-kidney-rejection Press release of the German Center for Infection Research (DZIF)
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