The mycobiome and clinical outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation.
Pneumology, Thoracic Surgery
Final Report Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potential cure for several hematological diseases, such as acute leukemias or lymphomas. During the process of allo-HCT, conditioning regimens and preventive antimicrobial treatments induce profound changes of the intestinal bacterial microbiota, which in turn are associated with clinical outcomes. In contrast to their bacterial counterparts, the dynamics of intestinal fungi and their clinical impact in patients undergoing allo-HCT have not yet been fully elucidated. To fill this knowledge gap, I incorporated high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing, fungal cultures of 1,279 fecal samples, and clinical data from a cohort of 156 patients undergoing a first allo-HCT. I could show that there were no global trends in the dynamics of intestinal fungal biomass and fungal diversity. Strikingly, the species composition changed remarkably from day to day in many instances. However, a subset of patients had a stable expansion of Candida parapsilosis complex species in their guts over several days (n = 19). Expansion of C. parapsilosis was associated with a decreased bacterial biomass. Future studies have to test the hypothesis that C. parapsilosis growth is restricted by high bacterial biomass. Intriguingly, patients with C. parapsilosis expansion had worse overall survival and higher transplant-related mortality than patients without C. parapsilosis expansion. These results are the largest longitudinal study on the mycobiota in patients undergoing allo-HCT to date and point to potential targets – increasing the bacterial biomass (or precent its decrease) and inhibiting fungal expansion – to improve patient outcomes.
Publications
- High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis. Nat Med. 2020 Jan;26(1):59-64
Zhai B, Ola M, Rolling T, Tosini NL, Joshowitz S, Littmann ER, Amoretti LA, Fontana E, Wright RJ, Miranda E, Veelken CA, Morjaria SM, Peled JU, van den Brink MRM, Babady NE, Butler G, Taur Y, Hohl TM
(See online at https://doi.org/10.1038/s41591-019-0709-7) - Determinants of COVID-19 disease severity in patients with cancer. Nat Med. 2020 Aug;26(8):1218-1223
Robilotti EV, Babady NE, Mead PA, Rolling T, Perez-Johnston R, Bernardes M, Bogler Y, Caldararo M, Figueroa CJ, Glickman MS, Joanow A, Kaltsas A, Lee YJ, Lucca A, Mariano A, Morjaria S, Nawar T, Papanicolaou GA, Predmore J, Redelman-Sidi G, Schmidt E, Seo SK, Sepkowitz K, Shah MK, Wolchok JD, Hohl TM, Taur Y, Kamboj M
(See online at https://doi.org/10.1038/s41591-020-0979-0) - Minority report: the intestinal mycobiota in systemic infections. Curr Opin Microbiol. 2020 Aug; 56:1-6
Rolling T, Hohl TM, Zhai B
(See online at https://doi.org/10.1016/j.mib.2020.05.004) - Customization of a dada2-based pipeline for fungal Internal Transcribed Spacer I (ITS 1) amplicon datasets. JCI Insight. 2021
Rolling T, Zhai B, Frame J, Hohl TM, Taur Y
(See online at https://doi.org/10.1172/jci.insight.151663) - Haematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species. Nat Microbiol. 2021 Nov 11
Rolling T, Zhai B, Gjonbalaj M, Tosini N, Yasuma-Mitobe K, Fontana E, Amoretti LA, Wright RJ, Ponce DM, Perales MA, Xavier JB, van den Brink MRM, Markey KA, Peled JU, Taur Y, Hohl TM
(See online at https://doi.org/10.1038/s41564-021-00989-7)
