Circulating blood microbiome signatures in patients with liver cirrhosis: Association between clinical parameters, circulating taxa and inflammatory cytokines

Abstract

Aim of the Study: To assess structure of circulating microbiome in patients with liver cirrhosis. Introduction: Intestinal microbiome to plays a significant role in the course of liver disease. Several studies have shown specific circulating microbiome profiles in patients with liver disease. We have aimed to assess circulating microbiome in patients with various degrees of portal hypertension (PH) and look for possible correlation with inflammatory cytokines and intestinal permeability markers. Methods: Study was conducted in Department of Gastroenterology of Lithuanian University of Health Sciences, Kaunas Clinics. 58 patients with liver cirrhosis and 46 healthy control (HC) subjects were enrolled. 16S rRNA gene sequencing was used to determine bacterial composition of blood plasma samples. Levels of IL-6, IL-8, LPS and FABP2 were measured in cirrhotics and HC subjects. Results: Blood microbiome in both PH patients and HC subjects was predominated by Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes. α-diversity was significantly higher in cirrhotic patients. Bacterial community structure showed a significant clustering between HC and PH patients. Genus Prevotella was associated with higher degree of portal hypertension and worse liver function, while abundance of Escherichia/Shigella – with liver function. Levels of IL-6 and IL-8 correlated with Child-Turcotte- Pugh and MELD scores, while FABP2 – with PH level and MELD score, LPS discriminated cirrhotics and HC. Several taxa correlated with these markers. Conclusions: Cirrhotic patients have distinct circulating microbiome profile. Levels of Prevotella and Escherichia/Shigella correlated with clinical parameters of liver cirrhosis. Several taxa correlated with inflammatory cytokines and intestinal permeability markers.