Gastrointestinal acute graft versus host disease: a translational perspective from pathogenesis to precision prevention and treatment.

Allo-HSCT represents a curative option for various hematological disorders. However, aGVHD remains the leading cause of non-relapse mortality following transplantation. The gastrointestinal tract is the most severely affected and prognostically unfavorable target organ in aGVHD, driven by donor T-cell-mediated epithelial damage, microbiota dysbiosis-driven immune amplification, and a self-perpetuating cycle of barrier disruption. Recent multi-omics studies have identified key pathogenic mechanisms, including microbiota-driven MHC-II expression and immunomodulation by microbial metabolites. Biomarker-driven risk stratification using the MAGIC algorithm has shifted management toward precision medicine, while targeted agents such as ruxolitinib, vedolizumab, and microbiota-directed interventions are reshaping therapeutic strategies. Novel interventional modalities, including FMT, recombinant LCN2, and specific bile acids, have forged innovative avenues that synergize microbiota-directed approaches with immunomodulation for the prevention and treatment of GI-aGVHD. This review systematically delineates the latest advances in the pathogenesis, risk stratification, and therapeutic strategies for GI-aGVHD, and envisions future directions for precision medicine centered on personalized microbiota-immune interventions.