Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX.
Hepatology. 2018 Oct;68(4):1549-1558. doi: 10.1002/hep.30037. Epub 2018 Sep 20.
UNLABELLED: Patients with cirrhosis are often exposed to antibiotics that can lead to resistance and fungal overgrowth. The role of fecal microbial transplant (FMT) in restoring gut microbial function is unclear in cirrhosis. In a Food and Drug Administration-monitored phase 1 clinical safety trial, patients with decompensated cirrhosis on standard therapies (lactulose and rifaximin) were randomized to standard-of-care (SOC, no antibiotics/FMT) or 5 days of broad-spectrum antibiotics followed by FMT from a donor enriched in Lachnospiraceae and Ruminococcaceae. Microbial composition (diversity, family-level relative abundances), function (fecal bile acid [BA] deconjugation, 7α-dehydroxylation, short-chain fatty acids [SCFAs]), and correlations between Lachnospiraceae, Ruminococcaceae, and clinical variables were analyzed at baseline, postantibiotics, and 15 days post-FMT. FMT was well tolerated. Postantibiotics, there was a reduced microbial diversity and autochthonous taxa relative abundance. This was associated with an altered fecal SCFA and BA profile. Correlation linkage changes from beneficial at baseline to negative after antibiotics. All of these parameters became statistically similar post-FMT to baseline levels. No changes were seen in the SOC group. CONCLUSION: In patients with advanced cirrhosis on lactulose and rifaximin, FMT restored antibiotic-associated disruption in microbial diversity and function. (Hepatology 2018; 00:000-000).
目的:在接受乳果糖和利福昔明标准治疗的失代偿期肝硬化患者中,评估粪便微生物移植(FMT)对恢复肠道微生物功能的作用。
方法:在一项经食品和药物管理局监测的 1 期临床安全性试验中,随机分配接受标准治疗(乳果糖和利福昔明)的失代偿期肝硬化患者至标准治疗(SOC,无抗生素/FMT)或 5 天广谱抗生素治疗后,接受富含lachnospiraceae 和 ruminococcaceae 的供体 FMT。在基线、抗生素后和 FMT 后 15 天,分析微生物组成(多样性、科水平相对丰度)、功能(粪便胆汁酸[BA]去结合、7α-羟化、短链脂肪酸[SCFA])以及lachnospiraceae、ruminococcaceae 与临床变量之间的相关性。
结果:FMT 耐受性良好。抗生素后,微生物多样性和自生分类群相对丰度降低。这与粪便 SCFA 和 BA 谱的改变有关。抗生素后,相关性从基线时的有益转变为负面。所有这些参数在 FMT 后均恢复到与基线水平统计学相似。SOC 组未见变化。
结论:在接受乳果糖和利福昔明治疗的晚期肝硬化患者中,FMT 恢复了抗生素相关的微生物多样性和功能紊乱。
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