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Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis
Jasmohan S. Bajaj, … , Masoumeh Sikaroodi, Patrick M. Gillevet
Jasmohan S. Bajaj, … , Masoumeh Sikaroodi, Patrick M. Gillevet
Published March 8, 2018
Citation Information: JCI Insight. 2018;3(5):e98019. https://doi.org/10.1172/jci.insight.98019.
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Clinical Medicine Hepatology

Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis

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Abstract

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. TRIAL REGISTRATION. NCT01458990. FUNDING. VA Merit I0CX001076.

Authors

Jasmohan S. Bajaj, Leroy R. Thacker, Andrew Fagan, Melanie B. White, Edith A. Gavis, Phillip B. Hylemon, Robert Brown, Chathur Acharya, Douglas M. Heuman, Michael Fuchs, Swati Dalmet, Masoumeh Sikaroodi, Patrick M. Gillevet

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Figure 2

DNA comparison of compensated versus decompensated cirrhosis.

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DNA comparison of compensated versus decompensated cirrhosis.
Histograms...
Histograms of linear discriminant analysis (LDA) effect size (LEfSe) comparison between stool microbiota at the genus level between compensated-cirrhosis patients (n = 92) and patients with decompensated cirrhosis (n = 2). Decompensation in cirrhosis is defined as hepatic encephalopathy, ascites, jaundice, and variceal bleeding. Log-level changes in LDA score are displayed on the x axis. (A) DNA analysis comparison. (B) RNA analysis comparison. Green bars: taxa found in greater relative abundance in decompensated cirrhosis. Red bars: taxa found in greater relative abundance in patients with compensated cirrhosis.
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