Drug-Induced Gastrointestinal and Hepatic Injury Across the Gut–Liver Axis: Mechanisms, Translational Biomarkers, and Pharmacological Protection

Adverse drug reactions affecting the gastrointestinal (GI) tract and liver represent two of the most significant, and frequently co-occurring, limitations in modern pharmacotherapy. Drug-induced liver injury (DILI) remains a leading cause of acute liver failure and late-stage drug attrition, and GI toxicity, ranging from epithelial barrier disruption to microbiota dysregulation, ranks among the most common dose-limiting side effects of widely prescribed medications. These two toxicity domains are not independent: the gut–liver axis creates a bidirectional communication network in which drug-induced GI damage amplifies hepatic exposure to luminal toxins and inflammatory mediators, and hepatic dysfunction in turn compromises intestinal homeostasis. Yet research has largely advanced in parallel silos, with mechanistic and clinical work rarely bridging both compartments simultaneously.This Research Topic is designed to address that cross-organ gap. While the field has established strong foundations in DILI mechanisms and hepatic therapeutics, translational biomarkers capable of detecting early, concurrent injury across the GI tract and liver remain scarce, and pharmacological strategies that protect both organ systems in an integrated manner remain an area of active investigation. A broad spectrum of agents contributes to this burden: NSAIDs and analgesics compromise GI mucosal integrity while exerting hepatotoxic effects; anticancer therapies damage both the intestinal epithelium and hepatic parenchyma; environmental xenobiotics disrupt both systems through persistent oxidative stress and inflammatory activation. The shared mechanistic substrate and the anatomical continuity of the gut–liver axis make a cross-organ research framework both scientifically justified and clinically relevant.This Research Topic invites original research, systematic reviews, and perspective articles that advance our mechanistic and translational understanding of drug-induced toxicity across the gut–liver axis. We particularly encourage contributions that bridge mechanism characterization with biomarker discovery, or that link toxicity profiling with protective pharmacological intervention across both organ compartments. Submissions should have a primary pharmacological framing, with a drug or xenobiotic as the causative agent; papers addressing gut–liver disease pathophysiology without a drug-induced context fall outside this topic’s scope. Topics of interest include, but are not limited to:- Molecular mechanisms of drug-induced toxicity across the gut–liver axis, including oxidative stress, mitochondrial dysfunction, inflammatory signaling, and regulated cell death pathways examined in both GI and hepatic contexts- Drug-induced disruption of the intestinal epithelial barrier and gut microbiota, and downstream consequences for hepatic function via gut–liver axis communication- Cross-organ biomarker identification and validation for early, concurrent detection of GI and hepatic drug injury across drug classes, bridging preclinical and clinical settings- Comparative toxicity profiles of NSAIDs, chemotherapeutic agents, and environmental xenobiotics across both GI and hepatic compartments, with emphasis on shared versus organ-specific injury pathways- Pharmacological, nutritional, and natural compound-based strategies to prevent or mitigate drug-induced injury simultaneously across the GI tract and liver- Gut–liver crosstalk as a target for protective interventions: bile acid signalling, microbial metabolites, mucosal immunity, and portal circulation dynamics- In vitro, ex vivo, in vivo, and organ-on-chip models that recapitulate the gut–liver interface for integrated drug toxicity researchBy integrating mechanistic insight, cross-organ biomarker research, and protective intervention strategies within a unified gut–liver axis framework, this collection aims to address a translational gap that single-organ approaches to drug toxicology have not yet bridged, with the goal of informing safer and more effective pharmacotherapy. Topic editors: Mihaela Liana Fericean, Mohamed Abdo, Ahmed Abdeen Source: https://www.frontiersin.org/research-topics/81653/drug-induced-gastrointestinal-and-hepatic-injury-across-the-gut-liver-axis-mechanisms-translational-biomarkers-and-pharmacological-protection