Objective:

To summarize recent advances in the pathogenesis, risk stratification, and therapeutic strategies for gastrointestinal acute graft-versus-host disease (GI-aGVHD).

Approach:

• Pathogenesis Insights: The article discusses the classical three-phase model of aGVHD pathogenesis and highlights the role of the intestinal microenvironment, including dysbiosis and epithelial injury, as well as the involvement of microbial metabolites in modulating host immunity.
• Therapeutic Strategies: Emerging therapies such as ruxolitinib, vedolizumab, and fecal microbiota transplantation (FMT) are being explored, alongside novel interventional modalities that synergize microbiota-directed approaches with immunomodulation.

Key Findings:

• The gastrointestinal tract is the most severely affected organ in aGVHD, exhibiting the highest rate of non-relapse mortality due to donor T-cell-mediated epithelial damage.
• Dysbiosis and epithelial barrier disruption create a vicious cycle that exacerbates T-cell-mediated injury, with microbial metabolites playing a significant role.
• Novel interventional modalities, including microbiota-directed approaches and specific bile acids, are being explored for prevention and treatment.

Interpretation:

The review highlights the significance of the microbiota-immune axis in GI-aGVHD management and the potential for precision medicine.

Limitations:

• The review may not cover all recent studies or emerging therapies beyond those mentioned.
• Potential biases in the studies referenced may affect the conclusions drawn.

Conclusion:

The article highlights the shift towards precision medicine in GI-aGVHD management, focusing on microbiota-immune interventions.