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Pre-transplant recovery of microbiome diversity without recovery of the original microbiome

Bone Marrow Transplantation volume 54, pages 1115–1117 (2019)Cite this article

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A typical treatment path for many patients with acute leukemia (AL) includes multiple rounds of chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Extensive antibiotic exposure, prolonged and repeated healthcare facility contact, nutritional changes, and gut barrier damage in these patients result in major disruptions in the gut microbial communities [1, 2]. Gut dysbiosis has been associated with adverse HCT outcomes including infection [3,4,5], graft-versus-host disease [6, 7], and mortality [8,9,10].

Diversity, typically defined by the Shannon diversity index (SDI) [11], is commonly used as an indicator of microbiome “health”. However, this definition is limited because microbial communities with the same level of diversity may have vastly different compositions with different impacts on the host. After repeated courses of antibiotics, the gut microbiome in healthy individuals usually regains its original diversity but sometimes stabilizes in a different steady state [12]. Although the long-term consequences of such microbiome shifts are unclear, their occurrence highlights the limitations of SDI when used as a sole descriptor of the microbiome. We hypothesized that in the setting of HCT, the pre-conditioning microbiome may be diverse but have a different configuration from its original state before chemotherapy for the underlying hematologic malignancy. In other words, diversity may mask a failure of microbiome recovery to its original state. We suspected that prolonged exposure to multiple antibiotics during intensive chemotherapy exemplifies sustained, compounded ecosystem perturbations, contrasting with the previously reported scenario of pulse disturbance (e.g., brief exposure to a single antibiotic) [13]. Compounded perturbations often yield unanticipated consequences for the microbial ecosystem [14].

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Acknowledgements

A University of Minnesota Medical School Innovation grant (to AR), a University of Minnesota Foundation grant (to AR), and funding from Achieving Cures Together and Hubbard Foundation supported this research. We thank Markas Welke, Andrea Hoeschen and Kevin Olson for coordinating sample collections. Sequence data were processed and analyzed using the resources of the Minnesota Supercomputing Institute.

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  1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Armin Rashidi, Shernan G. Holtan & Daniel J. Weisdorf

  2. Department of Surgery, University of Minnesota, Minneapolis, MN, USA

    Thomas Kaiser & Christopher Staley

  3. BioTechnology Institute, University of Minnesota, St. Paul, MN, USA

    Thomas Kaiser, Alexander Khoruts & Christopher Staley

  4. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Alexander Khoruts

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  1. Armin Rashidi
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Correspondence to Armin Rashidi.

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Rashidi, A., Kaiser, T., Holtan, S.G. et al. Pre-transplant recovery of microbiome diversity without recovery of the original microbiome. Bone Marrow Transplant 54, 1115–1117 (2019). https://doi.org/10.1038/s41409-018-0414-z

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