The gut microbiome in solid-organ and haematopoietic-stem-cell transplantation

Solid-organ transplantation (for example, kidney or liver) and haematopoietic-stem-cell transplantation have revolutionized treatment of end-stage organ failure and haematological malignancies. However, long-term outcomes are often undermined by complications such as allograft rejection, graft-versus-host disease in haematopoietic-stem-cell recipients, opportunistic infections, adverse effects of drugs and decreased quality of life. Emerging evidence now highlights the gut microbiome and its metabolites (such as short-chain fatty acids) as a potentially modifiable factor influencing transplantation outcomes. Transplantation recipients frequently exhibit gut dysbiosis, which has been linked to graft function, risk of infection (for example, vulnerability to multidrug-resistant bacteria), immune-mediated complications and patient survival. Furthermore, pharmacomicrobiomics studies indicate that microorganisms can metabolize immunosuppressive drugs into less active forms (such as the conversion of the immunosuppressive drug tacrolimus into less active or toxic forms through keto-reduction, glucuronidation or deconjugation) or can activate prodrugs (such as the conversion of mycophenolate mofetil into mycophenolic acid), thereby modulating drug efficacy and safety. Here, we discuss how the intestinal ecosystem is altered and persistently shaped by transplantation-related factors and immunosuppression and how these changes correlate with clinical outcomes. We provide a perspective on leveraging microbiome insights, through biomarkers or microbiome-targeted interventions, to improve outcomes in solid-organ and stem-cell transplantation.