Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders

Elena Biagi, Daniele Zama, Simone Rampelli, Silvia Turroni, Patrizia Brigidi, Clarissa Consolandi, Marco Severgnini, Eleonora Picotti, Pietro Gasperini, Pietro Merli, Nunzia Decembrino, Marco Zecca, Simone Cesaro, Maura Faraci, Arcangelo Prete, Franco Locatelli, Andrea Pession, Marco Candela, Riccardo Masetti

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number49
JournalBMC Medical Genomics
Volume12
Issue number1
DOIs
Publication statusPublished - Mar 7 2019

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Hematopoietic Stem Cell Transplantation
Cell Transplantation
Graft vs Host Disease
Fusobacterium
Pediatrics
Gastrointestinal Microbiome
rRNA Genes
Observational Studies
Ecosystem
Transplantation
Steroids
Therapeutics

Keywords

  • 16S rRNA gene sequencing
  • Acute graft-versus-host disease
  • Alloreactivity
  • Gut microbiota
  • Hematopoietic stem cell transplantation
  • Pediatric patients

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders. / Biagi, Elena; Zama, Daniele; Rampelli, Simone; Turroni, Silvia; Brigidi, Patrizia; Consolandi, Clarissa; Severgnini, Marco; Picotti, Eleonora; Gasperini, Pietro; Merli, Pietro; Decembrino, Nunzia; Zecca, Marco; Cesaro, Simone; Faraci, Maura; Prete, Arcangelo; Locatelli, Franco; Pession, Andrea; Candela, Marco; Masetti, Riccardo.

In: BMC Medical Genomics, Vol. 12, No. 1, 49, 07.03.2019.

Research output: Contribution to journalArticle

Biagi, E, Zama, D, Rampelli, S, Turroni, S, Brigidi, P, Consolandi, C, Severgnini, M, Picotti, E, Gasperini, P, Merli, P, Decembrino, N, Zecca, M, Cesaro, S, Faraci, M, Prete, A, Locatelli, F, Pession, A, Candela, M & Masetti, R 2019, 'Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders', BMC Medical Genomics, vol. 12, no. 1, 49. https://doi.org/10.1186/s12920-019-0494-7
Biagi, Elena ; Zama, Daniele ; Rampelli, Simone ; Turroni, Silvia ; Brigidi, Patrizia ; Consolandi, Clarissa ; Severgnini, Marco ; Picotti, Eleonora ; Gasperini, Pietro ; Merli, Pietro ; Decembrino, Nunzia ; Zecca, Marco ; Cesaro, Simone ; Faraci, Maura ; Prete, Arcangelo ; Locatelli, Franco ; Pession, Andrea ; Candela, Marco ; Masetti, Riccardo. / Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders. In: BMC Medical Genomics. 2019 ; Vol. 12, No. 1.
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abstract = "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.",
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AU - Biagi, Elena

AU - Zama, Daniele

AU - Rampelli, Simone

AU - Turroni, Silvia

AU - Brigidi, Patrizia

AU - Consolandi, Clarissa

AU - Severgnini, Marco

AU - Picotti, Eleonora

AU - Gasperini, Pietro

AU - Merli, Pietro

AU - Decembrino, Nunzia

AU - Zecca, Marco

AU - Cesaro, Simone

AU - Faraci, Maura

AU - Prete, Arcangelo

AU - Locatelli, Franco

AU - Pession, Andrea

AU - Candela, Marco

AU - Masetti, Riccardo

PY - 2019/3/7

Y1 - 2019/3/7

N2 - 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.

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KW - Pediatric patients

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