[Induction and regulation of intestinal graft-versus-host disease by the intestinal microbiota]

The intestinal microbiota is an important prognostic factor for allogeneic hematopoietic stem cell transplantation (allo-HCT), and decreased diversity of the intestinal microbiota is linked to shorter overall survival, high transplant-related mortality, and acute graft-versus-host disease (GVHD). Major factors that alter the intestinal microbiota during allo-HCT are broad-spectrum antibiotics and intestinal GVHD. Broad-spectrum antibiotics dysregulate the immune system and impair intestinal epithelial regeneration by reducing beneficial commensal bacteria and activating mucus-degrading bacteria, which disrupts the colonic barrier function. Intestinal GVHD leads to decreased secretion of antimicrobial peptides into the intestinal lumen, as well as mitochondrial dysfunction in the intestinal epithelium, altering the intestinal microbiota. Various therapeutic approaches targeting the intestinal microbiota have been investigated in clinical trials. Protecting the intestinal microbiota may further enhance the safety and efficacy of allo-HCT by regulating intestinal immune responses, promoting intestinal epithelial regeneration, and facilitating the production of beneficial metabolites derived from commensal bacteria.