Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally derived stool donor is safe in recurrent HE compared to SOC alone. An open-label, randomized clinical trial with a 5-month follow-up in outpatient men with cirrhosis with recurrent HE on SOC was conducted with 1:1 randomization. FMT-randomized patients received 5 days of broad-spectrum antibiotic pretreatment, then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow-up occurred on days 5, 6, 12, 35, and 150 postrandomization. The primary outcome was safety of FMT compared to SOC using FMT-related serious adverse events (SAEs). Secondary outcomes were adverse events, cognition, microbiota, and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed until study end. FMT with antibiotic pretreatment was well tolerated. Eight (80%) SOC participants had a total of 11 SAEs compared to 2 (20%) FMT participants with SAEs (both FMT unrelated; P = 0.02). Five SOC and no FMT participants developed further HE (P = 0.03). Cognition improved in the FMT, but not the SOC, group. Model for End-Stage Liver Disease (MELD) score transiently worsened postantibiotics, but reverted to baseline post-FMT. Postantibiotics, beneficial taxa, and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout. Conclusion: FMT from a rationally selected donor reduced hospitalizations, improved cognition, and dysbiosis in cirrhosis with recurrent HE. (Hepatology 2017;66:1727–1738)

中文翻译：

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来自理性大便供体的粪便微生物群移植改善肝性脑病：一项随机临床试验

尽管有标准的微生物菌群异常（SOC），但复发性肝性脑病（HE）是再次入院的主要原因。粪便微生物菌群移植（FMT）可以改善营养不良。但是，尚未在HE中对其进行研究。我们旨在确定与单独使用SOC相比，使用合理衍生的粪便供体的FMT在复发性HE中是否安全。一项开放标签的随机临床试验，以1：1的比例对门诊肝硬化合并HE复发的门诊男性进行了为期5个月的随访。FMT随机分组的患者接受了5天的广谱抗生素预处理，然后是来自同一供体的单次FMT灌肠，其中灌输了最佳的微生物菌群。随访发生在随机后第5、6、12、35和150天。与使用FMT相关的严重不良事件（SAE）的SOC相比，主要结果是FMT的安全性。次要结果是不良事件，认知，微生物群和代谢组学变化。在所有基线标准上，两组的参与者均相似，并且一直随访至研究结束。使用抗生素预处理的FMT耐受性良好。八名（80％）的SOC参与者总共有11名SAE，而2名（20％）的FMT参与者具有SAE（两者均无关）；P = 0.02）。5名SOC且无FMT参与者进一步发展了HE（P = 0.03）。在FMT中，认知度有所提高，但SOC组则没有。终末期肝病模型（MELD）评分在抗生素后暂时恶化，但在FMT后恢复为基线。变形杆菌的滋生会导致后抗生素，有益的生物分类和微生物多样性的降低。但是，FMT增加了多样性和有益的分类群。SOC微生物群和MELD评分在整个过程中保持相似。结论：合理选择的供体的FMT减少了复发性HE肝硬化的住院率，认知度和病情。（肝病学， 2017年； 66：1727–1738）