Drug-induced liver injury (DILI) is an adverse hepatic reaction with a complex etiopathogenesis, involving direct cellular damage by the drug, immune-mediated mechanisms, and host and environmental factors. The gut microbiota has recently been recognized as a key player in human physiopathology. In DILI, animal models and patients have shown significant alterations in gut microbiota composition. Evidence indicates that patients with DILI often present intestinal barrier dysfunction, characterized by increased permeability and the translocation of pathogen-associated molecular patterns (PAMPs) to the liver. This process may contribute to the onset or aggravation of liver injury by triggering harmful immune responses. Furthermore, dysbiosis can alter bacterial metabolite production, thereby affecting intestinal and hepatic homeostasis. The gut microbiota can also modify the efficacy and toxicity of drugs on an individual level, thereby increasing the risk of DILI. This review provides an overview of the current evidence on the mechanisms by which the gut microbiota contributes to inflammation, immune recruitment, and exacerbation of liver damage in DILI. A more in-depth understanding of how the gut microbiota alters intestinal and hepatic homeostasis is essential for advancing our knowledge of DILI pathogenesis, integrating novel biomarkers into clinical practice, and developing microbiota-based interventions.

Drug-induced liver injury  /  Hepatotoxicity  /  DILI  /  Gut–liver axis  /  Gut microbiota  /  Bacterial metabolites  /  Intestinal barrier  /  Immune system