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

Abstract

Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.

Traditional Chinese medicine, liver fibrosis, intestinal flora: is there any connection?—a narrative review

“…Imbalances in the intestinal flora and hyperproliferation of these microorganisms can lead to the destruction of the intestinal barrier. Because the intestinal flora flows into the liver through the portal vein (46), disruptions of the intestinal flora lead to immune responses in the liver and aggravated liver fibrosis occurrence and development (47). However, homeostasis of the intestinal flora supports the stability of the immune system (48).…”

Comparison of gut microbiota in male MAFLD patients with varying liver stiffness

“…Various liver diseases, including alcoholic liver disease, nonalcoholic liver disease, and primary sclerosing cholangitis, are associated with an altered microbiome ( Tilg et al., 2016 ). Furthermore, studies have shown that dysbiosis can increase toxic metabolites, cause liver inflammation and damage, aggravate liver disease, promote disease progression to liver fibrosis, and seriously affect patient outcomes ( Beraza, 2019 ; Zhou et al., 2019 ; Qin et al., 2021 ). These studies have predominantly focused on advanced liver fibrosis; however, there are few studies that have analyzed changes in the gut microbiota in the early stages of liver fibrosis.…”

Gut microbiome dysbiosis in patients with hepatitis B virus-related hepatocellular carcinoma after extended hepatectomy liver failure

“…The imbalanced BA metabolism increases intestinal permeability or decreases the production of SCFAs via the bridging function of the gut-liver axis, altering the gut microbiome composition and stimulating fibrogenesis, together with immune response activation in the graft. Thus, the gut microbiome can be considered a new therapeutic target for improving the longterm survival rates after liver transplantation (31).…”