In the healthy situation (A), intestinal homeostasis is maintained by a delicate balance between factors derived from the diet and metabolized by commensal bacteria, such as indoles and short-chain fatty acids (SCFAs) that suppress autoreactive T cells and stimulate epithelial barrier function (directly via upregulation of type 1 IFN and via IL-22) and production of defensins and antimicrobial peptides (AMPs) that suppress outgrowth of pathogenic bacteria. In allo-HSCT (B), chemotherapy and radiotherapy damage the intestinal epithelium and the microbiome directly and indirectly by negatively affecting dietary intake. Neutropenia necessitates the use of antibiotics, which also damages the microbiome. Together, these factors disrupt the homeostatic balance of the intestine, which leads to inflammation, the influx of alloreactive T cells (T) and neutrophils (N), mucositis, bacterial translocation, and GVHD.