Gut Microbiota Dysbiosis in Advanced Chronic Kidney Disease and Kidney Transplantation: A Narrative Review of Pathophysiological Mechanisms, Implications for Nutritional Status, and Biotic Interventions

Chronic kidney disease (CKD) is a serious public health issue affecting 10% of the global population. CKD is associated with intestinal dysbiosis, characterized by a reduction in saccharolytic bacteria and an increase in proteolytic genera that produce uremic toxins. This may promote intestinal barrier impairment (“leaky gut” syndrome), chronic low-grade inflammation, and protein-energy wasting (PEW), although most of the supporting evidence is observational. Kidney transplantation (KT) improves survival but may not fully reverse dysbiosis. KT recipients are exposed to residual uremia, use of perioperative antibiotics, and chronic immunosuppressive regimens. Drugs such as mycophenolate mofetil can cause gastrointestinal toxicity and reduced intake due to diarrhea or enteropathy, whereas corticosteroids and calcineurin inhibitors induce hyperphagia, hypomagnesemia, and insulin resistance. These factors may lead to a spectrum of complications ranging from persistent PEW in the early post-transplant period to a higher prevalence of weight gain and obesity, sarcopenia, and post-transplant diabetes. Furthermore, the microbiota may modulate pharmacological responses; in experimental and small clinical studies, genera such as Faecalibacterium have been linked to alterations in the metabolism of tacrolimus, potentially altering its therapeutic levels and the risk of nephrotoxicity or rejection. Interventions using biotics (prebiotics, probiotics, and synbiotics) are emerging as a potential adjuvant strategy to restore eubiosis and mitigate PEW. In non-dialysis and dialysis CKD patients, some biotics have been reported to reduce uremic toxins and inflammatory cytokines (IL-6, TNF-α), although results are heterogeneous. However, there is no evidence available regarding its ability to improve nutritional status following a KT. Safety data are limited, although biotic interventions are generally considered safe. Future prospective studies are required to confirm their efficacy and immunological safety, as well as any possible association with infectious adverse events.