粪菌移植有助于恢复经抗生素破坏的菌群


Title:
Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis is Restored by Fecal Transplant

DOI:
10.1002/hep.30037

Abstract:
Cirrhotic patients are often exposed to antibiotics that can lead to resistance and fungal overgrowth. The role of fecal microbial transplant (FMT) to restore gut microbial function is unclear in cirrhosis. In an FDA-monitored Phase 1 clinical safety trial, decompensated cirrhotic patients 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 acids (BA) deconjugation, 7α-dehydoxylation, short-chain fatty acids (SCFA)] and correlations between Lachnospiraceae, Ruminococcaceae and clinical variables were analyzed at baseline, post-antibiotics and 15 days post-FMT. FMT was well-tolerated. Post-antibiotics, there was a reduced microbial diversity and autochthonous taxa relative abundance. This was associated with an altered fecal SCFA and BA profile. Correlation linkages changes from beneficial at baseline to negative after antibiotics. All these parameters became statistically similar post-FMT to baseline levels. No changes were seen in the SOC group.In patients with advanced cirrhosis on lactulose and rifaximin, FMT restored antibiotic-associated disruption in microbial diversity and function. This article is protected by copyright. All rights reserved.

All Authors:
Jasmohan S Bajaj, Genta Kakiyama, Tor Savidge, Hajime Takei, Zain A Kassam, Andrew Fagan, Edith A Gavis, William M Pandak, Hiroshi Nittono, Phillip B Hylemon, Prapaporn Boonma, Anthony Haag, Douglas M Heuman, Michael Fuchs, Binu John, Masoumeh Sikaroodi, Patrick M Gillevet

First Authors:
Jasmohan S Bajaj

Correspondence:
Jasmohan S Bajaj

 摘要:

       接受标准治疗的失代偿肝硬化患者随机分入两组,试验组使用5天广谱抗生素,之后进行单次粪菌移植(FMT);供体菌群中毛螺菌科和疣微菌科富集,患者对FMT耐受性良好;抗生素治疗后,患者菌群多样性和丰度下降,伴随着粪便中短链脂肪酸显著减少、初级和结合胆汁酸增加、次级胆汁酸减少等变化;这些参数在FMT后恢复到接近抗生素治疗前的水平; 在接受标准治疗的晚期肝硬化患者中,FMT有助于恢复抗生素对菌群多样性和功能的不良影响。          

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