Efficacy and Safety of Probiotics and Synbiotics in Liver Transplantation

Abstract

This article summarizes available literature regarding the utilization of probiotic and synbiotics in liver transplant (LTX) recipients, reviewing efficacy in both decreasing infectious complications and immunomodulation, as well as exploring safety concerns. Data suggest that the use of probiotics containing Lactobacillus spp, either alone or in combination with prebiotics (referred to as synbiotics), may be effective in reducing infectious complications after LTX, a major contributor to graft loss, hospital length of stay, and mortality. Literature evaluating the use of probiotics to induce tolerance, reduce rejection, and prevent damage associated with ischemia-reperfusion injury is limited to animal models but compelling, as it suggests the use of probiotics may augment deleterious immune-mediated processes in this population. While the benefits of probiotics should be weighed against potential risks, these concerns are largely theoretical in the LTX recipient, with the majority of evidence extrapolated from case reports in other immunosuppressed populations. Based on available literature, it may be prudent to avoid products containing Saccharomyces sp, as these were not used in the efficacy studies, and the majority of the adverse event reporting stems from the use of products containing this organism. Further evaluation of the safety and efficacy of probiotic therapy is warranted. Studies specifically designed to elucidate the optimal product and initiation scenario and delineate safety in this population are needed to allow expanded use of this inexpensive, relatively nontoxic, and potentially beneficial therapeutic option after LTX.

Effects of both Pro- and Synbiotics in Liver Surgery and Transplantation with Special Focus on the Gut–Liver Axis—A Systematic Review and Meta-Analysis

“…Due to a dysbiosis with a decrease of beneficial bacteria and an increase of pathogenic species, the response to the host consists of higher endotoxin levels and increased bacterial translocation. Previous studies suggest that the intestinal microbiota regulate liver tumorigenesis or inflammatory reactions through altering the activity of pro-inflammatory microorganism-associated molecular patterns, bacterial metabolites, natural killer (NK) T cells-mediated bile acid metabolism, and prostaglandin (PG)E2- mediated suppression of antitumor immunity [ 61 , 63 , 64 , 65 ]. In the liver, lipopolysaccharides (LPS) can be inactivated by activation of the enzyme alkaline phosphatase by special bacterial strains (e.g., lactococcus lactis W19).…”

Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation

“…Perioperative administration of probiotics in patients undergoing liver transplantation is being increasingly recognized as a preventive measure against postoperative infections [19][20][21][22][23][24]26 . While one previous randomized trial assessed the effects of continuous pre-transplant probiotic intake on early post-transplant outcomes, the longterm consequences of such intervention remained unknown 24 .…”

The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

“…In another randomized controlled study, children receiving VSL#3 (a mixture of 8 probiotic strains) once daily for 4 months showed significant improvement in fatty liver disease severity, and a substantial reduction in BMI (Alisi et al 2014). In transplant-related studies, administration of probiotics and prebiotics has beneficially impacted the liver graft in the short term (Jorgenson et al 2018;Rayes et al 2002). Pre-LT probiotic/prebiotic use reduced the postoperative infection rate as well as the length of hospitalization and of antibiotic use, based on a metaanalysis of four controlled studies (Sawas et al 2015).…”