Functional Microbiomics in Liver Transplantation: Identifying Novel Targets for Improving Allograft Outcomes

Gut dysbiosis, defined as a maladaptive gut microbial imbalance, has been demonstrated in patients with end-stage liver disease (ESLD), defined as a contributor to disease progression, and associated clinically with severity of disease and liver-related morbidity and mortality. Despite this well recognized phenomena in patients with ESLD, the impact of gut dysbiosis and its rate of recovery following liver transplantation (LT) remains incompletely understood. The mechanisms by which alterations in the gut microbiota impact allograft metabolism and immunity, both directly and indirectly, are multifactorial and reflect the complexity of the gut-liver axis. Importantly, while research has largely focused on quantitative and qualitative changes in gut microbial composition, changes in microbial functionality (in the presence or absence of compositional changes) are of critical importance. Therefore, in order to translate functional microbiomics into clinical practice, one must understand not only the compositional, but also, the functional changes associated with gut dysbiosis and its resolution post-LT. In this review, we will summarize critical advances in functional microbiomics in liver transplant recipients as they apply to immune-mediated allograft injury, posttransplant complications, and disease recurrence while highlighting potential areas for microbial-based therapeutics in liver transplant recipients. Corresponding Author: Michael Kriss, MD, 12700 E. 19th Ave., Campus Box B146, Aurora, CO 80045. Email: Michael.Kriss@ucdenver.edu. Office: 303-724-1030 Authorship Page: Authorship: Michael Kriss, MD – participated in writing of the manuscript, participated in revision and final review of the manuscript Elizabeth C Verna, MD, MS – participated in revision and final review of the manuscript Hugo R Rosen, MD – participated in revision and final review of the manuscript Catherine A Lozupone, PhD – participated in revision and final review of the manuscript Disclosures: The authors declare no conflicts of interest Funding (relative to work reviewed): Michael Kriss, MD – Supported by NIH/NCATS Colorado CTSA Grant Number UL1 TR002535. Contents are the authors' sole responsibility and do not necessarily represent official NIH views. Elizabeth C Verna, MD, MS – Supported by NIH Grant Number K23 DK101827 Catherine A Lozupone, PhD – Supported by NIH Grant Numbers R01 DK104047, RO1 DK108366, and RO1 HL138639 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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