Impact of calcineurin inhibitors on gut microbiota: Focus on tacrolimus with evidence from in vivo and clinical studies.

Eur J Pharmacol

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address:

Published: December 2024

AI Article Synopsis

  • Calcineurin Inhibitors (CNIs), such as tacrolimus and cyclosporine A, are essential immunosuppressive drugs used in organ transplants to prevent graft rejection but may lead to gut dysbiosis, affecting immunity and metabolism.
  • Gut dysbiosis resulting from CNI use can cause adverse effects like hyperglycemia, nephrotoxicity, and diarrhea, highlighting the need for interventions to restore microbial balance.
  • This review aims to summarize research on the impact of CNIs on gut microbiota and discuss potential therapeutic approaches, including probiotics and dietary supplements, to alleviate dysbiosis and its associated effects.

Article Abstract

Calcineurin Inhibitors (CNIs), including tacrolimus and cyclosporine A, are the most widely used immunosuppressive drugs in solid organ transplantation. Those drugs play a pivotal role in preventing graft rejection and reducing autoimmunity. However, recent studies indicate that CNIs can disrupt the composition of gut microbiota or result in "gut dysbiosis". This dysbiosis has been shown to be a significant factor in reducing host immunity by decreasing innate immune cells and impairing metabolic regulation, leading to lipid and glucose accumulation. Several in vivo and clinical studies have demonstrated a mechanistic link between gut dysbiosis and the side effects of CNI. Those studies have unveiled that gut dysbiosis induced by CNIs contributes to adverse effects such as hyperglycemia, nephrotoxicity, and diarrhea. These adverse effects of the induced gut dysbiosis require interventions to restore microbial balance. Probiotics and dietary supplements have emerged as potential interventions to mitigate the side effects of gut dysbiosis caused by CNIs. In this complex relationship between CNI treatment, gut dysbiosis, and interventions, several types of gut microbiota and host immunity are involved. However, the mechanisms underlying these relationships remain elusive. Therefore, the aim of this review is to comprehensively summarize and discuss the major findings from in vivo and clinical data regarding the impact of treatment with CNIs on gut microbiota. This review also explores interventions to mitigate dysbiosis for therapeutic approaches of the side effects of CNIs. The possible underlying mechanisms of CNIs-induced gut dysbiosis with or without interventions are also presented and discussed.

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http://dx.doi.org/10.1016/j.ejphar.2024.177176DOI Listing

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