Altered profile of human gut microbiome is associated with cirrhosis and its complications

Abstract

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.

The intestinal microbiota and its role in human health and disease

“…A high fat diet was shown to affect the composition of gut microbiota through modifying the expression of bacterial genes responsible for nutrient uptake and adaptation to environmental change in the host intestine (66). A dysbiotic intestinal environment contributes to the pathogenesis of liver diseases (67,68). Also, Schnabl and Brenner (68) showed a correlation between altered intestinal microbiota and nonalcoholic fatty liver disease/steatohepatitis.…”

Bloodstream infections in patients with liver cirrhosis

“…31 In addition progressive intestinal dysbiosis was identified in patients with LC especially in advanced stages of the disease. 32 Interestingly, drugs that may alter the microbiota (i.e proton pomp inhibitors) or that affect the intestinal mobility (b-blockers) can have a role modifying the rate of bacterial infections in this setting. 33 The alterations in intestinal barrier permeability along with local immune dysfunction play a key role in determining an increase in bacterial translocation.…”

The role of microbiota in hepatic encephalopathy

“…15 In a larger study of 219 cirrhotic patients, the ratio of the autochthonous (commensal and potentially beneficial bacteria) 16 taxa (Ruminococcaceae, Lachnospiraceae, and clostridiales cluster XIV) to the non-autochthonous ones (Enterobacteriaceae and Bacteroidaceae) called the "cirrhosis dysbiosis ratio" was also correlated with MELD score and with endotoxin. 17 Therefore the disappearance of "good" bacteria and the increased relative abundance of potentially pathogenic ones could shift the microbiota into dysbiosis and negative consequences such as HE. The relative composition of bacteria remained similar in cirrhotic patients whose liver disease remains stable over several months.…”

“…The relative composition of bacteria remained similar in cirrhotic patients whose liver disease remains stable over several months. 17 Therefore, since most studies have included HE patients who have higher MELD scores than those without HE, it is important to further analyze these results in the context of overall disease severity in a longitudinal design.…”