The impact of the gut microbiome on liver transplantation

Abstract

Purpose of review Although gut dysbiosis can hasten disease progression in end-stage liver disease and contribute to disease severity, morbidity and mortality, its impact during and after transplant needs further study. Recent findings Changes in the microbiome are associated with hepatic decompensation. Immune homeostasis is further disrupted during transplant and with immunosuppressants required after transplant. There is increasing evidence of the role of microbiota in peri and posttransplant complications. Summary Although transplant is highly successful with acceptable survival rates, infections, rejection, disease recurrence and death remain important complications. Prognostication and interventions involving the gut microbiome could be beneficial.

Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis

“…Liver transplantation is the only effective way to treat a variety of end-stage liver diseases ( 1 , 2 ), but rejection is still one of the important reasons leading to the failure of liver transplantation ( 3 ). Therefore, studying the mechanism of liver transplant rejection and inducing immune tolerance are the research hotspots in the field of organ transplantation ( 4 ).…”

Microbiome compositions and fecal metabolite concentrations predict post-operative infection in liver transplant recipients

“…Some patients develop acute, fulminant hepatitis over the course of days, while others progressively lose hepatic function over many years due to chronic, progressive fibrosis leading to cirrhosis and end stage complications. The wide range of microbiome compositions we and others have detected in LT cohorts (1–4) likely result from diversity of diseases leading to ESLD, differing treatments modalities, including exposure to antibiotics for infections such as spontaneous bacterial peritonitis and acquisition of antibiotic-resistant pathobionts. We demonstrate that targeted mass spectrometric analysis of fecal samples identify LT patients with partial to complete loss of metabolites that impact pathobiont fitness, host immune defenses, and mucosal barrier integrity.…”

“…Although reduced abundance of beneficial taxa and expansion of Enterococcus and Enterobacterales species are known to occur in chronic liver disease and LT patients, the consequences of these compositional shifts on the microbiota-derived metabolome remain undefined. (1)(2)(3)(4) We performed targeted GC-and LC-MS analyses for metabolites produced or modified by the gut microbiota on peri-transplant fecal samples from the LT patient cohort (Figure 2). Within the LT patient cohorts, relative amounts of butyrate, valerate, and hexanoate varied dramatically, with patients in the low and medium diversity cohorts having markedly reduced levels while those in the high diversity group approached the range seen in the healthy donors.…”

“…An intact intestinal microbiome suppresses expansion of enteric pathogens, however patients with severe liver disease often have reduced microbiome diversity and increased density of antibiotic-resistant Enterococcus and Enterobacterales species. (1–4) Experimental models have demonstrated that metabolites produced by the intestinal microbiome, including short chain fatty acids (SCFAs), secondary bile acids and indole compounds, enhance host epithelial and immune defenses against enteric pathogens. (5–10) Microbiome derived metabolites likely contribute to resistance against infectious diseases in LT patients, however, this remains uninvestigated.…”

Role of the immune system in liver transplantation and its implications for therapeutic interventions

“…Preventing infections is crucial following LT. Alterations in the immune microenvironment and the use of immunosuppressants after the transplant can further disrupt the balance of the gut–liver axis and trigger an inflammatory response in liver immune cells 334 . Given the intricacies of immune balance, the comprehensive reduction of infection risk can be achieved through preoperative prevention and postoperative regulation.…”