Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease

Najla El Jurdi, Shernan G. Holtan, Andrea Hoeschen, Jessica Velguth, Benjamin Hillmann, Brian C. Betts, Margaret L. MacMillan, Daniel J. Weisdorf, Alexander Khoruts, Armin Rashidi, Robin Shields-Cutler

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The role of the gastrointestinal microbiome in predisposing to chronic graft-versus-host disease (cGVHD), an immune-mediated haematopoietic cell transplant (HCT) complication, is not well defined. We examined the relationship of the host faecal microbiome with subsequent cGVHD development by analysing baseline stool samples as well as post-HCT changes in microbiome composition and metabolite pathway analyses. We analysed pre-transplant baseline samples from 11 patients who subsequently developed cGVHD compared to 13 controls who did not develop acute GVHD or cGVHD at any time. We found a significant differential abundance of multiple taxa at baseline between cGVHD versus controls, including the Actinobacteria phylum and Clostridium genus. A subgroup analysis of longitudinal samples within each patient revealed a greater loss of alpha diversity from baseline to post-engraftment in patients who subsequently developed cGVHD. Metabolic pathways analysis revealed that two pathways associated with short-chain fatty acid metabolism were enriched in cGVHD patient microbiomes: β-oxidation and acyl-CoA synthesis, and γ-aminobutyrate shunt. In contrast, a tryptophan catabolism pathway was enriched in controls. Our findings show a distinct pattern of baseline microbiome and metabolic capacity that may play a role in modulating alloreactivity in patients developing cGVHD. These findings support the therapeutic potential of microbiome manipulation for cGVHD prevention.

Original languageEnglish (US)
Pages (from-to)288-294
Number of pages7
JournalBritish journal of haematology
Volume203
Issue number2
DOIs
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Keywords

  • allogeneic
  • chronic GVHD
  • haematopoietic cell transplantation
  • microbiome

PubMed: MeSH publication types

  • Journal Article

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