Opinion Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Oct 30, 2021; 11(2): 11-16
Published online Oct 30, 2021. doi: 10.5411/wji.v11.i2.11
Interactions between human microbiome, liver diseases, and immunosuppression after liver transplant
Milena Peruhova, Monika Peshevska-Sekulovska, Tsvetelina Velikova
Milena Peruhova, Monika Peshevska-Sekulovska, Department of Gastroenterology, University Hospital Lozenetz, Sofia 1407, Bulgaria
Milena Peruhova, Tsvetelina Velikova, Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
Tsvetelina Velikova, Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria
Author contributions: Peruhova M and Peshevska-Sekulovska M wrote the draft; Velikova T added additional sections and proofread the final version; All authors revised and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Milena Peruhova, MD, Assistant Professor, Chief Doctor, Department of Gastroenterology, University Hospital Lozenetz, Kozyak 1 str., Sofia 1407, Bulgaria. mperuhova@gmail.com
Received: May 9, 2021
Peer-review started: May 9, 2021
First decision: July 27, 2021
Revised: August 16, 2021
Accepted: October 13, 2021
Article in press: October 13, 2021
Published online: October 30, 2021
Abstract

In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.

Keywords: Liver transplantation, De novo malignancy, Immunosuppressive therapy, Calcineurin inhibitors, Tacrolimus, Cyclosporine, Microbiome, Carcinogenesis, Immune tolerance

Core Tip: Liver transplant recipients have a higher risk of developing de novo malignancy compared to the general population. Immunosuppressive therapy used after liver transplantation is a substantial risk factor for the development of de novo malignancy. Tumorigenesis in liver transplantation patients is linked to the length and intensity of immunosuppression. Data show that the microbiota could significantly affect the survival and acceptance of transplanted allographs. This once again indicates the incredibly complex interaction between the immune system and microbiome in the settings of liver transplantation and raises the possible strategies to induce immunotolerance and reduce complications such as de novo malignancy.