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Graft-Versus-Host Disease

Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors

Bone Marrow Transplantation volume 52, pages 1643–1650 (2017)Cite this article

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Abstract

Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient’s pre-conditioning microbiota nor the influence of the transplant donor’s microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors. On average, recipients had lower fecal bacterial diversity (P=0.0002) and different phylogenetic membership (UniFrac P=0.001) than the healthy transplant donors. Recipients with lower phylogenetic diversity had higher overall mortality rates (hazard ratio=0.37, P=0.008), but no statistically significant difference in agGvHD risk. In contrast, high bacterial donor diversity was associated with decreased agGvHD risk (odds ratio=0.12, P=0.038). Further investigation is warranted as to whether selection of hematopoietic stem cell transplant donors with high gut microbiota diversity and/or other specific compositional attributes may reduce agGvHD incidence, and by what mechanisms.

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Acknowledgements

We thank our study participants and clinical staff. We thank Jørgen V Bjørnholt, Merete Eggesbø, and Tore Midtvedt for use of their antibiotic classification scale in our sensitivity analysis and thank Keith Hazleton for consulting on antibiotic classifications. We are grateful for our anonymous peer reviewers for their feedback on our manuscript. This research was generously supported by the Amy Strelzer Manasevit Research Program and Denver Golfers Against Cancer.

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  1. C A Lozupone and V H Nguyen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biostatistics and Informatics, University of Colorado, Aurora, CO, USA

    C Liu

  2. Department of Medicine, University of Colorado, Aurora, CO, USA

    D N Frank, S Chau, D Ir, C A Lozupone & V H Nguyen

  3. Department of Medicine, University of Chicago, Chicago, IL, USA

    M Horch, E A Horch, K Tretina, K van Besien & V H Nguyen

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Correspondence to C A Lozupone.

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Liu, C., Frank, D., Horch, M. et al. Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors. Bone Marrow Transplant 52, 1643–1650 (2017). https://doi.org/10.1038/bmt.2017.200

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