Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders.
16S rRNA gene sequencing
Acute graft-versus-host disease
Alloreactivity
Gut microbiota
Hematopoietic stem cell transplantation
Pediatric patients
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
26
10
2018
accepted:
26
02
2019
entrez:
9
3
2019
pubmed:
9
3
2019
medline:
7
1
2020
Statut:
epublish
Résumé
The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset. Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and > 30 days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation. Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30. We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.
Sections du résumé
BACKGROUND
The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset.
METHODS
Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and > 30 days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation.
RESULTS
Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30.
CONCLUSIONS
We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.
Identifiants
pubmed: 30845942
doi: 10.1186/s12920-019-0494-7
pii: 10.1186/s12920-019-0494-7
pmc: PMC6404274
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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