Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant
Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant
复制标题
DOI：
10.1002/hep.30037
复制
发表时间：
2018-10-01
期刊：
影响因子：
13.5
通讯作者：
Gillevet, Patrick M.
中科院分区：
文献类型：
--
作者：
Bajaj, Jasmohan S.;Kakiyama, Genta;Gillevet, Patrick M.
肝硬化患者经常接触抗生素，这可能导致耐药性和真菌过度生长。粪便微生物移植（FMT）在肝硬化患者中恢复肠道微生物功能的作用尚不清楚。在美国食品和药物管理局监测的1期临床安全性试验中，接受标准治疗（乳果糖和利福昔明）的失代偿性肝硬化患者随机接受标准治疗（SOC，无抗生素/FMT）或5天的广谱抗生素治疗，然后接受来自富含毛螺菌科和瘤胃球菌科的供体的FMT。在基线、抗生素后和FMT后15天分析微生物组成（多样性、家族水平相对丰度）、功能（粪便胆汁酸[BA]去结合、7-脱羟基、短链脂肪酸[SCFA]）以及毛螺菌科、瘤胃球菌科和临床变量之间的相关性。FMT耐受性良好。抗生素后，有减少的微生物多样性和本地类群的相对丰度。这与粪便SCFA和BA特征改变有关。相关性连锁从基线时的有益变化为抗生素治疗后的阴性。所有这些参数在FMT后与基线水平在统计学上相似。SOC组未观察到变化。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恢复了微生物多样性和功能中与糖尿病相关的破坏。（Hepatology 2018; 00：000-000）。
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, 7-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).