The gut-liver axis refers to the bidirectional relationship between the gut and its
microbiota, and the liver, resulting from the integration of signals generated by
dietary, genetic and environmental factors. This reciprocal interaction is established
by the portal vein which enables transport of gut-derived products directly to the
liver, and the liver feedback route of bile and antibody secretion to the intestine.
The intestinal mucosal and vascular barrier is the functional and anatomical structure
that serves as a playground for the interactions between the gut and the liver, limiting
the systemic dissemination of microbes and toxins while allowing nutrients to access
the circulation and to reach the liver. The control of microbial communities is critical
to maintaining homeostasis of the gut-liver axis, and as part of this bidirectional
communication the liver shapes intestinal microbial communities. Alcohol disrupts
the gut-liver axis at multiple interconnected levels, including the gut microbiome,
mucus barrier, epithelial barrier and at the level of antimicrobial peptide production,
which increases microbial exposure and the proinflammatory environment of the liver.
Growing evidence indicates the pathogenetic role of microbe-derived metabolites, such
as trimethylamine, secondary bile acids, short-chain fatty acids and ethanol, in the
pathogenesis of non-alcoholic fatty liver disease. Cirrhosis by itself is associated
with profound alterations in gut microbiota and damage at the different levels of
defence of the intestinal barrier, including the epithelial, vascular and immune barriers.
The relevance of the severe disturbance of the intestinal barrier in cirrhosis has
been linked to translocation of live bacteria, bacterial infections and disease progression.
The identification of the elements of the gut-liver axis primarily damaged in each
chronic liver disease offers possibilities for intervention. Beyond antibiotics, upcoming
therapies centred on the gut include new generations of probiotics, bacterial metabolites
(postbiotics), faecal microbial transplantation, and carbon nanoparticles. FXR-agonists
target both the gut and the liver and are currently being tested in different liver
diseases. Finally, synthetic biotic medicines, phages that target specific bacteria
or therapies that create physical barriers between the gut and the liver offer new
therapeutic approaches.