Gut-Liver Axis Failure in Critical Alcohol-Associated Liver Disease: From ICU Secondary Hits to Microbiome-Targeted Therapy.

Alcohol-associated liver disease (ALD) can progress to critical illness phenotypes requiring intensive care, including severe alcohol-associated hepatitis, acute decompensation, and alcohol-associated acute-on-chronic liver failure (ACLF). In these patients, short-term outcomes are driven less by the burden of fibrosis alone than by systemic inflammation, immune dysfunction, infection, and multiorgan failure. At the core of this process is gut-liver axis failure, which links alcohol-induced dysbiosis and intestinal barrier disruption to microbial translocation, hepatic innate immune activation, and systemic inflammatory amplification. In the intensive care unit (ICU), secondary hits such as broad-spectrum antibiotics, acid suppression, parenteral nutrition, shock, sedatives or opioids, and mechanical ventilation may further exacerbate these mechanisms and disturb microbial ecology and barrier integrity. Microbiome-targeted therapies (probiotics, postbiotics, and fecal microbiota transplantation) are biologically plausible. However, current evidence is mainly derived from non-ICU or relatively stable ALD populations. Therefore, their use in critically ill patients requires strict safety boundaries, including severe barrier disruption, invasive devices, uncontrolled infections, and profound immune dysfunction. This narrative review synthesizes the pathophysiological continuum from gut barrier failure to systemic inflammation and multiorgan dysfunction in critical ALD, with particular emphasis on ICU-specific secondary hits, safety-aware microbiome modulation, and future phenotype-informed precision strategies.