Abstract
The role of the human microbiome in health and disease is becoming increasingly apparent. Emerging evidence suggests that the microbiome is affected by solid organ transplantation. Kidney transplantation is the gold standard treatment for End-Stage Renal Disease (ESRD), the advanced stage of Chronic Kidney Disease (CKD). The question of how ESRD and transplantation affect the microbiome and vice versa includes how the microbiome is affected by increased concentrations of toxins such as urea and creatinine (which are elevated in ESRD), whether restoration of renal function following transplantation alters the composition of the microbiome, and the impact of lifelong administration of immunosuppressive drugs on the microbiome. Changes in microbiome composition and activity have been reported in ESRD and in therapeutic immunosuppression, but the effect on the outcome of transplantation is not well-understood. Here, we consider the current evidence that changes in kidney function and immunosuppression following transplantation influence the oral, gut, and urinary microbiomes in kidney transplant patients. The potential for changes in these microbiomes to lead to disease, systemic inflammation, or rejection of the organ itself is discussed, along with the possibility that restoration of kidney function might re-establish orthobiosis.
Highlights
The human microbiome can confer multiple benefits to health (Wang et al, 2017)
This review considers evidence that microbiome composition is linked to outcome in kidney transplant surgery
Microbiome changes due to reduced kidney function in Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD) may be exacerbated during transplantation, with associated immunosuppression and restoration of kidney function
Summary
The human microbiome can confer multiple benefits to health (Wang et al, 2017). Examples include aiding development of organs (Goyal et al, 2015) and the innate and adaptive immune systems (Lee and Mazmanian, 2010; Honda and Littman, 2016; Thaiss et al, 2016) and resistance to infection (Bäumler and Sperandio, 2016). For example, has been associated with the immunosuppressant ciclosporin, and kidney-transplantation (Rateitschak-Plüss et al, 1983) where bacteria-induced inflammation could be affected by transplantdriven microbiome changes (Brown et al, 1991). Significant and persistent differences have been reported in kidney transplant recipients before and after transplant (Table 1) The potential for these changes to negatively impact patient health is suggested by increases in opportunistic pathogens, which has been reported even where concurrent differences in alpha-diversity and global community structure are not observed (Diaz et al, 2013). The source of infections within around one month of transplantation may be hositialacquired whereas those in the subsequent five months may be due TABLE 1 | Summary of recent studies reporting microbiome-associated differences (and their, potentially, related, post-operative effects) using kidney transplant recipient (KTR) cohorts. Ciclosporin, tacrolimus, azathioprine, mycophenolate mofetil, prednisolone Anti-thymocyte globulin, basiliximab, tacrolimus, belatacept, mycophenolate mofetil, prednisone
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