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Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation

Abstract

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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Fig. 1: Fungal microbiota and overall survival after alloHCT.
Fig. 2: Candida albicans impact DFS and GRFS after alloHCT.
Fig. 3: Forrest plot of Cox proportional hazards model for overall survival.

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Acknowledgements

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.

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F.M. designed the study, recruited patients, performed experimental work, collected, assembled and analyzed data, and wrote and revised the manuscript. A.L. analyzed data and performed statistical analysis. G.B. and R.M. recruited patients, collected and assembled data, and helped write the manuscript. R.D., E.B., and T.L., recruited patients, collected data and helped write the manuscript. S.J. and N.R. performed experimental work. B.G., H.S. and M.M. designed the study, supervised research, analyzed data and helped with writing the manuscript.

Corresponding author

Correspondence to Florent Malard.

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Competing interests

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

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