Table 1.
Microbial-metabolite pathways | Overview of bacterial transformation | Examples of clinical and translational investigations in liver disease |
---|---|---|
Bile acids | • Deconjugation: bile salt hydrolases • Secondary bile acid formation: 7α dehydroxylation • Epimerisation • Desulphation |
• Significant changes during alcohol-associated liver disease progression and alcohol cessation • Changes with use of FXR modulators, FMT or rifaximin |
Choline compounds (TMAO) | • Degraded by several taxa to TMA then oxidised in the liver to TMAO | • Associated with metabolic syndrome • Linked with minimal hepatic encephalopathy • Reduced pre-transplant but rebounds post-liver transplant |
Indole derivatives | • Balance between human and microbial tryptophan degradation • Specific taxa are unclear • Metabolites: tryptamine, indole-3-pyruvate, indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-aldehyde, indole-3-acetic acid, indole-3-lactic acid, indole acrylic acid and indole-3-propionic acid • Indole sulfation in the liver |
• Preclinical evidence of strengthening gut barrier with selected metabolites • High production of oxindole in patients with hepatic encephalopathy • Associated with mood changes that co-exist with liver disease • Higher in those who developed negative outcomes in cirrhosis in outpatient and inpatient setting |
Short-chain fatty acids | • Fermentation of dietary fibre and colonic mucus | • Varying impact on obesity and high-fat diet response • Butyrate levels reduce with advancing liver disease and alcohol-associated liver disease • Varies with lactulose administration • Restored/enhanced after FMT |
FMT, faecal microbiota transplant; FXR, farnesoid X receptor; TMAO, tri-methylamine oxide.