Targeting the gut-kidney axis to improve kidney transplantation prognosis: from mechanisms to clinical intervention strategies

Kidney transplantation is an important treatment for end-stage renal disease, but lifelong immunosuppression is needed to prevent immune rejection, but the immunosuppressive therapy increases the risk of post-transplant complications. Therefore, how to improve the long-term survival of transplanted kidneys and reduce rejection has become a hot spot in current research. Recently, the 'gut-kidney axis' has received widespread attention as an important pathway for immune regulation. It refers to the fact that changes in either side of the gastrointestinal tract and kidney will affect the other side through energy metabolism, immuno-inflammation, intestinal mucosa, intestinal flora, among others, up and including to adverse consequences, which can be mutually causative. With the theory of 'gut-kidney axis', more and more studies have found that intestinal immune cells and microbiota play an important role in maintaining immune homeostasis and regulating the immune microenvironment of renal transplant recipients. Some studies have found that intestinal immune cells and microbiota not only influence the systemic immune status, but also may regulate the immune response of transplanted kidneys through metabolites and inflammatory mediators. In this review, we summarize the potential mechanisms of intestinal immune cells and microbiota in immune tolerance and rejection after renal transplantation based on the theory of 'gut-kidney axis'. In addition, we highlight microbiome modulation strategies, particularly dietary interventions and fecal microbiota transplantation, as emerging approaches with potential to improve transplant outcomes. A deeper understanding of the mechanism of action of the gut-kidney axis will provide new ideas and therapeutic targets for immunomodulation after renal transplantation.