Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis
Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis
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DOI：
10.1172/jci.insight.98019
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发表时间：
2018-03-08
期刊：
影响因子：
8
通讯作者：
Gillevet, Patrick M.
中科院分区：
文献类型：
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作者：
Bajaj, Jasmohan S.;Thacker, Leroy R.;Gillevet, Patrick M.
背景。肝硬化与肠道微生物变化有关，但目前的16S rDNA技术可对死菌和活菌进行测序。我们的目的是将rRNA含量与来自同一粪便样本的DNA进行比较，以评估肝硬化进展并预测住院治疗。肝硬化患者和对照组提供粪便进行RNA和DNA分析。采用线性判别分析对肝硬化/对照组和肝硬化内（代偿/失代偿、感染/未感染、肾功能不全/未肾功能不全、利福昔明使用/未使用）的DNA和RNA细菌含量进行比较。另一组用奥美拉唑治疗14天，进行纵向微生物群评估。患者住院随访90天。建立了包含和不包含DNA和RNA微生物数据的临床数据的住院多变量模型。纳入26例对照组和154例肝硬化患者（54例感染，62例失代偿，20例肾功能不全，18例利福昔明）。RNA和DNA分析显示潜在致病类群不同，但原生类群组成相似。30名受试者接受了奥美拉唑的研究，证明了RNA和DNA变化之间的差异。36例患者在90天内住院。在RNA模型中，MELD评分和肠球菌独立预测住院，而在DNA模型中，MELD具有预测作用，Roseburia具有保护作用。在这两种模型中，添加微生物群显著增加了MELD评分对住院的预测。同一粪便样本的DNA和RNA分析显示不同的微生物群组成，独立预测肝硬化住院风险。肝硬化患者肠道微生物群的RNA和DNA含量随疾病严重程度、感染和奥美拉唑的使用而变化。
BACKGROUND. Cirrhosis is associated with gut microbial changes, but current 16S rDNA techniques sequence both dead and live bacteria. We aimed to determine the rRNA content compared with DNA from the same stool sample to evaluate cirrhosis progression and predict hospitalizations.METHODS. Cirrhotics and controls provided stool for RNA and DNA analysis. Comparisons were made between cirrhotics/controls and within cirrhosis (compensated/decompensated, infected/uninfected, renal dysfunction/not, rifaximin use/not) with respect to DNA and RNA bacterial content using linear discriminant analysis. A separate group was treated with omeprazole for 14 days with longitudinal microbiota evaluation. Patients were followed for 90 days for hospitalizations. Multivariable models for hospitalizations with clinical data with and without DNA and RNA microbial data were created.RESULTS. Twenty-six controls and 154 cirrhotics (54 infected, 62 decompensated, 20 renal dysfunction, 18 rifaximin) were included. RNA and DNA analysis showed differing potentially pathogenic taxa but similar autochthonous taxa composition. Thirty subjects underwent the omeprazole study, which demonstrated differences between RNA and DNA changes. Thirty-six patients were hospitalized within 90 days. In the RNA model, MELD score and Enterococcus were independently predictive of hospitalizations, while in the DNA model MELD was predictive and Roseburia protective. In both models, adding microbiota significantly added to the MELD score in predicting hospitalizations.CONCLUSION. DNA and RNA analysis of the same stool sample demonstrated differing microbiota composition, which independently predicts the hospitalization risk in cirrhosis. RNA and DNA content of gut microbiota in cirrhosis are modulated differentially with disease severity, infections, and omeprazole use.