Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients

Abstract

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5–12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.

The gut microbiome in solid organ transplantation

“…Currently, the findings are mostly limited to cross-sectional or longitudinal observational correlation studies on kidney and liver transplantation. Generally, there is a consensus that transplantation induces a trend towards an unbalanced, so-called dysbiotic gut microbiome, which is characterized by a loss of microbial diversity [34][35][36][37][38][39] and an increase in the Proteobacteria phylum. 35,37,39 Gut microbial changes seem to persist over time, with one study detecting dysbiosis up to 6 years after transplantation.…”

“…Generally, there is a consensus that transplantation induces a trend towards an unbalanced, so-called dysbiotic gut microbiome, which is characterized by a loss of microbial diversity [34][35][36][37][38][39] and an increase in the Proteobacteria phylum. 35,37,39 Gut microbial changes seem to persist over time, with one study detecting dysbiosis up to 6 years after transplantation. 39 Some studies suggested minor signs of recovery after the immediate post-transplant period, 36,38 but long-term diversity remained decreased.…”

Promises of Big Data and Artificial Intelligence in Nephrology and Transplantation

“…Those needs that are classified as unmet require provision of some ample spaces for the purpose of imagination in relation to leveraging the strength associated with big data, as well as relevant artificial intelligence (AI) to improve the overall status of patients with kidney diseases [25]. In this article, we discuss the big data concepts in nephrology, describe the potential use of AI in nephrology and transplantation, and also encourage researchers and clinicians to submit their invaluable research, including original clinical research studies [26][27][28][29][30], database studies from registries [31][32][33], meta-analyses [34][35][36][37][38][39][40][41][42][43][44], and artificial intelligence research [25,[45][46][47][48] in nephrology and transplantation. Table 1 demonstrates known and commonly used databases that have provided big data in nephrology and transplantation [49][50][51].…”

Urinary 3-hydroxyisovaleryl carnitine excretion, protein energy malnutrition and risk of all-cause mortality in kidney transplant recipients: Results from the TransplantLines cohort studies

“…Secondary analyses with sex-stratified tertiles of plasma biotin demonstrated that a low plasma biotin was independently associated with an increased risk of mortality. Potential causes for a low plasma biotin may be an insufficient nutrient intake or dysbiosis of the gut microbiota, which recently was demonstrated in KTR, most likely with chronic use of immunosuppressants as an important contributor [13]. Though biotin status has not been quantified in kidney transplants recipients before, it is known that transplant recipients are prone to vitamin deficiencies, including vitamin B6, vitamin K, vitamin C and vitamin B3 [28,56e58].…”

“…KTR also suffer from dysbiosis, a disruption in the balance of the gut microbiome, in the years following transplantation [13]. Due to the chronic usage of immunosuppressive medications and frequent usage of antibiotics, KTR may also be susceptible to deficiencies of vitamins produced by microbiota, including biotin [14,15].…”