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

Journal: Nature reviews. Cancer

This review article examines how the intestinal microbiome influences outcomes after allogeneic hematopoietic cell transplantation (allo-HCT), with a particular focus on graft-versus-host disease (GVHD).

Key points:

  • Microbiome–immune crosstalk: Preclinical studies demonstrate that gut microbes and their metabolites shape host immune responses after allo-HCT, influencing GVHD development and severity.
  • Mucosal barrier integrity: Specific microbial taxa are associated with preservation or breakdown of the intestinal epithelial barrier. Barrier disruption, in turn, amplifies inflammation and GVHD risk.
  • Microbial metabolites: Bacterial products such as short-chain fatty acids and other metabolites modulate immune cell function and may protect against or exacerbate GVHD, highlighting potential therapeutic targets.
  • Clinical impact of dysbiosis: Clinical data consistently show that loss of microbial diversity and overgrowth of pathogenic taxa (dysbiosis) are independent predictors of overall transplantation-related and GVHD-related mortality.
  • Therapeutic strategies under study: Ongoing trials are evaluating microbiota-directed interventions (e.g., strategies to prevent or reverse dysbiosis) to improve allo-HCT outcomes and mitigate GVHD.
  • Towards personalized care: The authors anticipate that integrating microbiome profiling with traditional clinical risk factors will enable more individualized risk stratification and tailored interventions in allo-HCT recipients.

Overall, the article synthesizes preclinical and clinical evidence to support the microbiome as both a biomarker and a modifiable therapeutic target in the allo-HCT setting.

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