Gut Microbiome Altered in Kidney Transplant Recipients

By Karen Blum

WASHINGTON, DC – Kidney transplant recipients have an imbalance of gut bacteria marked by a lower diversity of organisms and increased levels of Proteobacteriae such as Escherichia coli compared with healthy renal donors, according to new research presented at Kidney Week 2019.

The study, comparing composition of the gut microbiome in 139 renal transplant recipients and 105 healthy donors, found over 195 significant differences throughout the taxonomy, said lead author J.C. Swarte, PhD, of University Medical Centre Groningen in the Netherlands (Abstract SA-OR103). This included 37 significant differences at the genus level and 135 significant differences at the species level. Recipients who had diarrhea (n=28) had even lower gut diversity.

“In the field of renal transplantation, the microbiome has not yet been studied extensively,” Swarte said. “However, all recipients require immunosuppressive medications and antibiotic treatment, and they are known to change the gut microbiome. In addition, recipients suffer from diarrhea and previous studies have shown that this is associated with dysbiosis rather than infection.”

Swarte and colleagues analyzed the gut microbiome of these individuals, all participants in the TransplantLines Biobank, and Cohort Study, using 16s rRNA sequencing of fecal samples. They compared the composition among transplant recipients and healthy donors using MaAsLin: Multivariate Association with Linear Models. Transplant recipients had a mean age of 54.6 years and median time after transplantation was 1.08 years.

At the phylum level, transplant recipients had slightly lower levels of Firmicutes, the most abundant phylum of the gut microbiome, he said. This loss is accompanied by a significant increase in Proteobacteriae. At the species level, transplant recipients had significantly lower levels of Faecalibacterium prausnitzi, the most common gut bacteria. They also had a loss of butyrate-producing bacteria, short-chain fatty acids important for maintaining gut health.

Donor or recipient status, years since transplantation and presence of diarrhea were among the determinants found to significantly impact the variations. Medications such as proton pump inhibitors, tacrolimus, and mycophenolic acid also were strong determinants.

More research is needed to explain the differences and identify potential methods to strengthen the gut microbiome in recipients, senior study author Stephan J.L. Bakker, MD, PhD, told Kidney News Online. A follow-up study conducted by the group in 1,000 renal transplant recipients and 200 healthy controls is performing metagenomic sequencing to look at the taxa and composition with more power, and to study metabolic pathways in the gut. “We eventually hope to pinpoint targets where we could interfere,” Swarte said.

Another abstract presented by the group (#FR-OR128), in 152 renal transplant recipients and 77 healthy controls, found that the recipients had a significantly lower concentration of methane in the breath and a lower prevalence of Methanobrevibacter smithii in the feces. This archaeon, between a parasite and a bacteria, plays an important role in the digestion of complex sugars. Together, the findings indicate that transplant recipients have altered microbiota and altered gut microbial fermentation.


Resources

Abstract SA-OR103: “Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.”

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Karen Blum
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WASHINGTON, DC – Kidney transplant recipients have an imbalance of gut bacteria marked by a lower diversity of organisms and increased levels of Proteobacteriae such as Escherichia coli compared with healthy renal donors, according to new research presented at Kidney Week 2019.

The study, comparing composition of the gut microbiome in 139 renal transplant recipients and 105 healthy donors, found over 195 significant differences throughout the taxonomy, said lead author J.C. Swarte, PhD, of University Medical Centre Groningen in the Netherlands (Abstract SA-OR103). This included 37 significant differences at the genus level and 135 significant differences at the species level. Recipients who had diarrhea (n=28) had even lower gut diversity.

“In the field of renal transplantation, the microbiome has not yet been studied extensively,” Swarte said. “However, all recipients require immunosuppressive medications and antibiotic treatment, and they are known to change the gut microbiome. In addition, recipients suffer from diarrhea and previous studies have shown that this is associated with dysbiosis rather than infection.”

Swarte and colleagues analyzed the gut microbiome of these individuals, all participants in the TransplantLines Biobank, and Cohort Study, using 16s rRNA sequencing of fecal samples. They compared the composition among transplant recipients and healthy donors using MaAsLin: Multivariate Association with Linear Models. Transplant recipients had a mean age of 54.6 years and median time after transplantation was 1.08 years.

At the phylum level, transplant recipients had slightly lower levels of Firmicutes, the most abundant phylum of the gut microbiome, he said. This loss is accompanied by a significant increase in Proteobacteriae. At the species level, transplant recipients had significantly lower levels of Faecalibacterium prausnitzi, the most common gut bacteria. They also had a loss of butyrate-producing bacteria, short-chain fatty acids important for maintaining gut health.

Donor or recipient status, years since transplantation and presence of diarrhea were among the determinants found to significantly impact the variations. Medications such as proton pump inhibitors, tacrolimus, and mycophenolic acid also were strong determinants.

More research is needed to explain the differences and identify potential methods to strengthen the gut microbiome in recipients, senior study author Stephan J.L. Bakker, MD, PhD, told Kidney News Online. A follow-up study conducted by the group in 1,000 renal transplant recipients and 200 healthy controls is performing metagenomic sequencing to look at the taxa and composition with more power, and to study metabolic pathways in the gut. “We eventually hope to pinpoint targets where we could interfere,” Swarte said.

Another abstract presented by the group (#FR-OR128), in 152 renal transplant recipients and 77 healthy controls, found that the recipients had a significantly lower concentration of methane in the breath and a lower prevalence of Methanobrevibacter smithii in the feces. This archaeon, between a parasite and a bacteria, plays an important role in the digestion of complex sugars. Together, the findings indicate that transplant recipients have altered microbiota and altered gut microbial fermentation.


Resources

Abstract SA-OR103: “Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.”

Date:
Tuesday, November 12, 2019