Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients
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Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients. / Ilett, Emma E.; Jørgensen, Mette; Noguera-Julian, Marc; Nørgaard, Jens Christian; Daugaard, Gedske; Helleberg, Marie; Paredes, Roger; Murray, Daniel D.; Lundgren, Jens; MacPherson, Cameron; Reekie, Joanne; Sengeløv, Henrik.
I: Blood advances, Bind 4, Nr. 22, 2020, s. 5797-5809.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients
AU - Ilett, Emma E.
AU - Jørgensen, Mette
AU - Noguera-Julian, Marc
AU - Nørgaard, Jens Christian
AU - Daugaard, Gedske
AU - Helleberg, Marie
AU - Paredes, Roger
AU - Murray, Daniel D.
AU - Lundgren, Jens
AU - MacPherson, Cameron
AU - Reekie, Joanne
AU - Sengeløv, Henrik
PY - 2020
Y1 - 2020
N2 - Acute graft-versus-host disease (aGVHD) is a leading cause of transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). 16S ribosomal RNA (16S rRNA) gene-based studies have reported that lower gut bacterial diversity and the relative abundance of certain bacteria after aHSCT are associated with aGVHD. Using shotgun metagenomic sequencing and a large cohort, we aimed to confirm and extend these observations. Adult aHSCT recipients with stool samples collected from day 230 to day 100 relative to aHSCT were included. One sample was selected per patient per period (pre-aHSCT (day 230 to day 0), early post-aHSCT (day 1 to day 28), and late post-aHSCT (day 29 to day 100)), resulting in 150 aHSCT recipients and 259 samples. Microbial and clinical factors were tested for differences between time periods and an association with subsequent aGVHD. Patients showed a decline in gut bacterial diversity posttransplant, with several patients developing a dominance of Enterococcus. A total of 36 recipients developed aGVHD at a median of 34 days (interquartile range, 26-50 days) post-aHSCT. Lower microbial gene richness (P 5.02), a lower abundance of the genus Blautia (P 5.05), and a lower abundance of Akkermansia muciniphila (P 5.01) early post-aHSCT was observed in those who developed aGVHD. Myeloablative conditioning was associated with aGVHD along with a reduction in gene richness and abundance of Blautia and A muciniphila. These results confirm low diversity and Blautia being associated with aGVHD. Crucially, we add that pretransplant conditioning is associated with changes in gut microbiota. Investigations are warranted to determine the interplay of gut microbiota and conditioning in the development of aGVHD.
AB - Acute graft-versus-host disease (aGVHD) is a leading cause of transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). 16S ribosomal RNA (16S rRNA) gene-based studies have reported that lower gut bacterial diversity and the relative abundance of certain bacteria after aHSCT are associated with aGVHD. Using shotgun metagenomic sequencing and a large cohort, we aimed to confirm and extend these observations. Adult aHSCT recipients with stool samples collected from day 230 to day 100 relative to aHSCT were included. One sample was selected per patient per period (pre-aHSCT (day 230 to day 0), early post-aHSCT (day 1 to day 28), and late post-aHSCT (day 29 to day 100)), resulting in 150 aHSCT recipients and 259 samples. Microbial and clinical factors were tested for differences between time periods and an association with subsequent aGVHD. Patients showed a decline in gut bacterial diversity posttransplant, with several patients developing a dominance of Enterococcus. A total of 36 recipients developed aGVHD at a median of 34 days (interquartile range, 26-50 days) post-aHSCT. Lower microbial gene richness (P 5.02), a lower abundance of the genus Blautia (P 5.05), and a lower abundance of Akkermansia muciniphila (P 5.01) early post-aHSCT was observed in those who developed aGVHD. Myeloablative conditioning was associated with aGVHD along with a reduction in gene richness and abundance of Blautia and A muciniphila. These results confirm low diversity and Blautia being associated with aGVHD. Crucially, we add that pretransplant conditioning is associated with changes in gut microbiota. Investigations are warranted to determine the interplay of gut microbiota and conditioning in the development of aGVHD.
U2 - 10.1182/bloodadvances.2020002677
DO - 10.1182/bloodadvances.2020002677
M3 - Journal article
C2 - 33232475
AN - SCOPUS:85097236044
VL - 4
SP - 5797
EP - 5809
JO - Blood advances
JF - Blood advances
SN - 2473-9529
IS - 22
ER -
ID: 258829867