The Cirrhosis Dysbiosis Ratio defines Changes in the Gut Microbiome Associated with Cirrhosis and its Complications

By J. Bajaj, D. Heuman, P. Hylemon, A. Sanyal, Melanie B White, Pamela Monteith, Nicole A. Noble, A. Unser, Kalyani Daita, Andmorgan R. Fisher and 2 more. Journal of Hepatology, 2013

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Background & Aims The gut microbiome is altered in cirrhosis; however its evolution with disease progression is partly understood. We aimed to study changes in microbiome over cirrhosis severity, its stability over time and its longitudinal alterations with decompensation. Methods Controls and age-matched cirrhotics (compensated/decompensated/hospitalized) were included. Their stool microbiota was quantified using multi-tagged pyrosequencing. Ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio(CDR); a low number indicating dysbiosis. Firstly, microbiome was compared between controls and cirrhotic sub-groups. Second, for stability assessment, stool collected twice within 6 months in compensated outpatients was analyzed. Thirdly, changes after decompensation were assessed using (a) longitudinal comparison in patients before/after hepatic encephalopathy development (HE), (b) longitudinal cohort of hospitalized infected cirrhotics MELD-matched to uninfected cirrhotics followed for 30 days. Results 244 subjects [219 cirrhotics (121 compensated outpatients,54 decompensated outpatients,44 inpatients) and 25 age-matched controls)] were included. CDR was highest in controls(2.05) than compensated(0.89), decompensated(0.66) and inpatients(0.32,p<0.0001) and negatively correlated with endotoxin. Microbiota and CDR remained unchanged in stable outpatient cirrhotics (0.91 vs. 0.86, p=0.45). In patients studied before/after HE development, dysbiosis occurred post-HE(CDR:1.2 to 0.42, p=0.03). In the longitudinal matched-cohort, microbiota were significantly different between infected/uninfected cirrhotics at baseline and a low CDR was associated with death and organ failures within 30 days. Conclusions Progressive changes in the gut microbiome accompany cirrhosis and become more severe in the setting of decompensation. The cirrhosis dysbiosis ratio may be a useful quantitative index to describe microbiome alterations accompanying cirrhosis progression.

Subfields: Epidemiology, Hepatology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8268d82fb07740673b9d92a7a803e525022903bb

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Citations in the corpus

Bile Acids and the Gut Microbiome (2014, background): “Unau 0267-1379 2014 Wolters Kluwer Health | Lippincott Williams & Wilk dysbiosis was characterized by significant reduction in gram-positive members of the normal microbiota such as Blautia and Ruminococcaceae [9].”
Gut microbiome based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease (2017, positive): “Bajaj and colleagues conducted studies in a diverse group of patients with cirrhosis with or without hepatic decompensation and assessed association with 16S profiling (Bajaj et al., 2014).”
Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma (2018, background): “14 Recent studies in animal models indicate that the intestinal microbiota promote HCC development through the gut microbiota-liver axis.”
Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives (2020, background): “Together with the typical severely compromised gut barrier, gut dysbiosis promotes cirrhosis inflammatory state due to hepatic accumulation of PAMPs and toxic bacteria products [123] and correlates with liver disease progression [124,125].”