The intestinal microbiota as a key modulator of acute graft-versus-host disease

Abstract

Although allogeneic haematopoietic cell transplantation (allo-HCT) is a curative therapy for various malignant diseases, severe complications such as graft-versus-host disease (GVHD) limit its use. The intestinal microbiome has long been known to modulate allo-HCT outcomes. Studies in the past two decades alone have uncovered a complex interplay between the microbial repertoire and the host immune system during allo-HCT. Preclinical studies have characterized the crosstalk between the microbiome and the immune response of the host, discovered associations between microbial taxa and the integrity of the mucosal intestinal barrier, and investigated the role of microbial metabolites in GVHD. Clinical studies have demonstrated that dysbiosis is an independent predictor of both transplantation-related and GVHD-related mortality, and ongoing trials are investigating microbiota-focused approaches to improve clinical outcomes and reduce GVHD severity after allo-HCT, paving the way for therapeutic applications of microbiome research. We anticipate that these insights will support the development of personalized therapies for patients receiving allo-HCT, integrating microbiome profiles with individual risk data. In this Review, we summarize current preclinical and clinical studies, providing a comprehensive account of translational efforts in this highly dynamic field. In this Review, Paredes et al. discuss preclinical and clinical evidence suggesting that the intestinal microbiome influences outcomes of allogeneic haematopoietic cell transplantation and, in particular, graft-versus-host disease and propose that microbiota-focused approaches may improve these clinical outcomes.