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.

肝移植 (LT) 是终末期肝病患儿的一种挽救生命的选择。然而，约 50% 的患者在 LT 后 1 年内发生移植物纤维化，肝功能正常。移植物纤维化可能发展为肝硬化，导致移植物功能障碍并最终需要重新移植。以前的研究已经确定了 LT 后纤维化的各种危险因素，然而，迄今为止，这些因素似乎都不能完全解释移植物纤维化的原因。最近，关于肠道微生物组在实体器官移植结果中的重要作用的证据已经积累。由于患有终末期肝病的儿科患者中存在改变的微生物组，我们假设微生物组成或功能的持续改变有助于移植物纤维化的发展，例如，由于肠道通透性增加、胆汁酸代谢失衡和/或短链脂肪酸 (SCFA) 产量减少导致的细菌易位。随后，可以在移植物中激活免疫反应，同时刺激纤维发生。在这里，我们回顾了目前关于微生物组成或功能改变可能导致儿童 LT 移植物纤维化的潜在机制的知识，并对肠道微生物组操作作为缓解移植物纤维化和改善长期移植物纤维化的治疗目标的功效提供了前瞻性观点。 LT 后的长期存活率。与纤维化的刺激一起。在这里，我们回顾了目前关于微生物组成或功能改变可能导致儿童 LT 移植物纤维化的潜在机制的知识，并对肠道微生物组操作作为缓解移植物纤维化和改善长期移植物纤维化的治疗目标的功效提供了前瞻性观点。 LT 后的长期存活率。与纤维化的刺激一起。在这里，我们回顾了目前关于微生物组成或功能改变可能导致儿童 LT 移植物纤维化的潜在机制的知识，并对肠道微生物组操作作为缓解移植物纤维化和改善长期移植物纤维化的治疗目标的功效提供了前瞻性观点。 LT 后的长期存活率。