Abstract
In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species (Stenotrophomonas pavanii, Methylobacterium extorquens) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a ‘functional dysbiosis’ in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE.
Highlights
Compositional shifts in the gut microbiota are linked with liver disease[1,2]
Among the bacterial species able to translocate across the hepatic barrier (Fig. 3), we found that Stenotrophomonas pavanii and Methylobacterium extorquens in the peripheral blood raised the risk of hepatic encephalopathy (HE) by 135% and 142%, respectively, while Clostridium indolis lowered it by 10%, performing a protective role (Table 3)
A caveat of our study would be the use of bacterial DNA as a bacterial translocation (BT) marker, which raises the question of the role of resident bacteria in both portal and peripheral blood[35]
Summary
In liver cirrhosis (LC), the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria and a decrease in beneficial commensal species[3]. Bacterial fragments and byproducts reach the liver through the portal system and contribute to a condition of chronic inflammation that is involved in the development of many complications in cirrhotic patients[4,5]. To outline the impact of the gut microbiota on LC and its physiopathological implications, we used the integration of omics platforms[18] to describe the microbial compositional shifts in caecal biopsies, faeces, and peripheral and portal blood from LC patients, relating them to clinical parameters
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