Gut-Liver Axis and Microbiome in Advanced Chronic Liver Disease

The Gut-Liver Axis in Advanced Chronic Liver Disease

 

Cirrhosis of the liver can be complicated by decompensating features, which portend worsening survival. These include the development of jaundice, synthetic failure with coagulopathy and hypoalbuminaemia, and portal hypertension leading to ascites, variceal haemorrhage, and/or hepatic encephalopathy, and. The causes for decompensation that lead to advanced chronic liver disease (ACLD) and the development of superimposed organ failure – termed acute-on-chronic liver failure (ACLF) – are related to pathological changes that occur affecting the ‘gut-liver axis’ in cirrhosis. ACLF causes very high short-term mortality (up to 65% at 28 days) and is thought to be triggered by undiagnosed infections in the majority of cases.

 

The liver is intimately linked anatomically to the gut via the portal vein, and exposure to the gut microbiota (bacteria, fungi, viruses, etc) and their metabolites translocating across the gut lumen will impact upon the diseased liver, and further drive hepatic dysfunction and even enhance fibrosis progression. Several mechanisms are likely to conspire together as key elements in the pathogenesis of ACLD. Amongst these are (i) translocation of intestinal bacteria and their products including pathogen associated molecular patterns (PAMPs), (ii) gut barrier disruption and inflammation and (iii) local gut-specific, (iv) hepatic and (v) systemic innate and adaptive immune pathway dysfunction with (vi) paradoxical systemic inflammation which in part is due to the production of danger-associated molecular patterns (DAMPs) which are endogenous inducers released by necrotic cells or as a result of extracellular matrix breakdown.

 

My group is focused on several work-streams focused on the gut-liver axis in ACLD:

1. Characterising the changes that occur in the oral and gut micro-/mycobiome in ACLD by metagenomic sequencing

2. Utilise novel markers to measure gut-derived bacterial translocation

3. Assess the intestinal barrier in cirrhosis (inflammatory and immune characterisation)

4. Profiling of microbiome generated metabolites e.g. plasma and faecal bile acids and by urinary NMR (working with Dr Jane Cox)

 

 

Published by: Foundation for Liver Research

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