Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS). While fungal diversity had no impact on patient outcomes, we observed that high versus low relative abundance of Candida albicans in alloHCT patients at day 0 was associated with a significantly lower OS, DFS and graft-versus-host-free, relapse-free survival (GRFS) (p = 0.0008, p = 0.0064 and p = 0.026, respectively). While these results are limited by low patient numbers and low fungal read counts in some samples, they suggest a potentially important role for C albicans in alloHCT.
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Malard, F., Gasc, C., Plantamura, E. & Dore, J. High gastrointestinal microbial diversity and clinical outcome in graft-versus-host disease patients. Bone Marrow Transplant. 53, 1493–1497 (2018).
Taur, Y. et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124, 1174–1182 (2014).
Peled, J. U. et al. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N. Engl. J. Med. 382, 822–834 (2020).
Stein-Thoeringer, C. K. et al. Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science 366, 1143–1149 (2019).
Holler, E. et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol. Blood Marrow Transplant. 20, 640–645 (2014).
Jenq, R. R. et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol. Blood Marrow Transplant. 21, 1373–1383 (2015).
Peled, J. U. et al. Intestinal microbiota and relapse after hematopoietic-cell transplantation. J. Clin. Oncol. 35, 1650–1659 (2017).
Legoff, J. et al. The eukaryotic gut virome in hematopoietic stem cell transplantation: new clues in enteric graft-versus-host disease. Nat. Med. 23, 1080–1085 (2017).
Sokol, H. et al. Fungal microbiota dysbiosis in IBD. Gut 66, 1039–1048 (2017).
Lemoinne S., et al. Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis. Gut 69, 92–102(2019).
Girmenia, C. et al. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol. Blood Marrow Transplant. 20, 872–880 (2014).
Uryu, H. et al. alpha-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice. Blood 125, 3014–3023 (2015).
van der Velden, W. J. et al. Role of the mycobiome in human acute graft-versus-host disease. Biol. Blood Marrow Transplant. 19, 329–332 (2013).
Limon, J. J. et al. Malassezia is associated with Crohn’s disease and exacerbates colitis in mouse models. Cell Host Microbe 25, 377–388.e376 (2019).
Aykut, B. et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574, 264–267 (2019).
Jawhara, S. et al. Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3. J. Infect. Dis. 197, 972–980 (2008).
Zuo, T. et al. Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection. Nat. Commun. 9, 3663 (2018).
Leonardi, I. et al. Fungal trans-kingdom dynamics linked to responsiveness to fecal microbiota transplantation (FMT) therapy in ulcerative colitis. Cell Host Microbe 27, 823–829 e823 (2020).
Zhang, F. et al. Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease. Nat. Commun. 12, 65 (2021).
Bacher, P. et al. Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176, 1340–55 e1315 (2019).
Sovran, B. et al. Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome 6, 152 (2018).
Samonis, G. et al. Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob. Agents Chemother. 37, 51–53 (1993).
Schmieder, R. & Edwards, R. Quality control and preprocessing of metagenomic datasets. Bioinformatics 27, 863–864 (2011).
Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
R. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/. 2020.
Kessy A., et al. UNITE QIIME release for Fungi. UNITE Community. https://doi.org/10.15156/BIO/786385 (2020).
Koljalg, U. et al. Towards a unified paradigm for sequence-based identification of fungi. Mol. Ecol. 22, 5271–5277 (2013).
McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One 8, e61217 (2013).
Therneau, T. M & Grambsch, P. M. Modeling survival data: extending the Cox model (Springer, New York, 2000).
Kassambara A., Kosinski M., Biecek P. survminer: Drawing Survival Curves using ‘ggplot2’. R package version 0.4.6. 2019.
Wickham H. ggplot2: elegant graphics for data analysis.; 2009.
Kassambara A. ggpubr: ‘ggplot2’ Based Publication Ready Plots. R package version 0.2.3. 2019.
The authors acknowledge the Association for Training, Education and Research in Hematology, Immunology and Transplantation for the generous and continuous support of the research work. We are grateful to Prof. Junia V. Melo (University of Adelaide, Australia) for critical reading of this manuscript. We thank Baptiste Lamarthée for his technical assistance and our nursing staff for offering the best care to our patients.
F.M. reports lecture honoraria from Therakos/Mallinckrodt, Janssen, Keocyte, Sanofi, JAZZ pharmaceuticals and Astellas, all outside the submitted work. H.S. received consultancy, or lecture fees from Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat Pharma, BiomX, Biose and Takeda, all outside the submitted work.; and is a co-founder of Exeliom bioscience. M.M. reports grants and lecture honoraria from Janssen, Sanofi, Maat Pharma and JAZZ pharmaceuticals, lecture honoraria from Celgene, Amgen, BMS, Takeda, and Pfizer, grants from Roche, all outside the submitted work. The other authors declare no competing financial interests.
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Malard, F., Lavelle, A., Battipaglia, G. et al. Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation. Mucosal Immunol (2021). https://doi.org/10.1038/s41385-021-00429-z