Microbiome: Impairment of gut microbial balance is linked to increased mortality following kidney and liver transplants.

Disruptions in the gut microbiome have been linked to lower survival rates in people who have had kidney and liver transplants, highlighting the critical importance of the vast and complex microbial communities that inhabit us.

Credit: Pixabay/CC0 Public Domain
Credit: Pixabay/CC0 Public Domain

Researchers in the Netherlands studied fecal samples from over 1,000 kidney and liver transplant recipients to learn how the balance of microbes in the gut microbiome affects post-transplant survival. Researchers discovered that gut microbiome dysbiosis (disruptions in microbial diversity) is associated with increased mortality after solid organ transplantation.

The gut microbiome contains both "good" and "bad" microbes, such as bacteria, viruses, and fungi. The healthy balance of these microbial communities in the gut provides health benefits throughout the body. The living communities, on the other hand, are not static; they change in response to diet, emotions, exercise, surgery, and medication exposure.

Previous research found that recipients of stem cell transplants had a higher mortality risk when their gut microbiome was disrupted. It has taken until now to ask, based on a large sample size, whether microbiota disruption has a negative impact on solid organ transplant recipients.

The Dutch team knew going into their research that the health of the microbiome influenced the outcomes of patients who had undergone stem cell transplants, also known as bone marrow transplants. The procedure provides the recipient with healthy progenitor cells from a donor in order to generate a new blood supply. However, scientists were aware that a successful stem cell transplant would be insufficient unless the gut microbiome flourished with a diverse population of beneficial microbes.

Researchers from the University of Groningen's medical center in Groningen, Netherlands, reported in Science Translational Medicine on the importance of microbial variety in ensuring a healthy transplant outcome.

"Organ transplantation is a life-saving treatment for patients with end-stage disease, but survival rates after transplantation vary significantly," wrote J. Casper Swarte, the report's first author. Swarte and colleagues, who worked with a large team of collaborators in the Netherlands, emphasized that stem cell transplants had long stood alone as evidence that gut health played a role in transplant success.

"Although there is growing evidence that the gut microbiome is linked to patient survival after hematopoietic cell transplantation, little is known about the gut microbiome's role in solid organ transplantation."

"We used shotgun metagenomic sequencing to assess microbial taxonomy, metabolic pathways, antibiotic resistance genes, and virulence factors in 1,370 fecal samples from 415 liver and 672 renal transplant recipients," Swarte explained.

The Dutch study, which included a two-year follow-up with some of the kidney transplant recipients, supports the importance of gut microbiota in transplant outcomes and suggests that microbiota-based therapies could help improve outcomes for more patients.

Swarte and colleagues also studied fecal samples from 1,183 controls to gain more information about the importance of the microbiome in post-transplant health. Overall, transplant recipients demonstrated classic signs of gut microbiome dysbiosis, indicating a disrupted microbiota that persisted for some as long as 20 years. This included less diverse gut bacteria and a higher prevalence of antibiotic resistance genes. Patients with the least bacterial diversity fared the worst in terms of survival.

Patients with evidence of gut microbiome dysbiosis had a 77% three-year survival rate, compared to 96% for patients with high bacterial diversity. The analysis also revealed that the use of immune-suppressing drugs, which are required to prevent organ rejection, was the most important factor causing disruptions in patients' gut microbiomes.

While the study suggests a link between solid organ transplants and gut microbiome dysbiosis, Swarte and colleagues caution that it does not prove a causal link. They also hope that future work will broaden their research to include heart and lung transplant recipients.

"Our data showed that both liver and kidney transplant recipients had gut dysbiosis, including lower microbial diversity, an increase in the abundance of unhealthy microbial species, a decrease in the abundance of important metabolic pathways, and an increase in the prevalence and diversity of antibiotic resistance genes and virulence factors," Swarte emphasized.

"Finally, we demonstrated that the use of immunosuppressive drugs was related to the observed dysbiosis, and that the extent of dysbiosis was related to increased mortality after transplantation." This study is a step toward potential microbiome-targeted interventions that could influence the outcomes of solid organ transplant recipients."

Journal information: Science Translational Medicine


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