Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy

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.

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

“…Using the metagenomics data, eight pathways were underrepresented and two overrepresented in LC. The authors concluded that intervention with prebiotics/probiotics/synbiotics, diet, or fecal microbiota transplant could support development of new customized treatments for LC patients [156]. Interestingly, partial reversal of dysbiosis and metabolomic profile was reported after splenectomy in LC patients (12) [157].…”

Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?

“…On a correlation network analysis, these overrepresented genera were linked to poor cognitive performance, disease severity (MELD scores), enhanced systemic inflammation (serum IL-17 levels), and endothelial activation (serum soluble intravascular adhesion molecule (sICAM-1) levels) [214]. Concomitant evaluations of microbiome in the cecal mucosa, feces, and peripheral/portal blood from patients with liver cirrhosis by another study group revealed that the portal blood had a bacterial community composition similar to that of the colonic mucosa, but not to that of the feces, strengthening the importance of mucosa-associated microbiota for studying pathophysiological meanings in liver cirrhosis [215]. Chen et al [216] examined the duodenal mucosal microbe and reported that Veillonella, Megasphaera, Dialister, Atopobium and Prevotella were increased in cirrhotic patients compared with healthy subjects whose duodenal mucosa enriched with Neisseria, Haemophilus and SR1 genera incertae sedis.…”

Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant

“…1,6,7 Enteropathy also increases bacterial translocation, with associated systemic inflammation that contributes to the hypercatabolic state. 8,9 Effective treatments to reverse malnutrition and sarcopenia in the face of deteriorating liver function have mostly remained elusive. In a limited number of studies where advancements in muscle mass or strength have been realised, significant improvements in mortality and clinical complications (hepatic encephalopathy, sepsis) have been described.…”