Journal Article

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

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

2019

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 16S rRNA gene sequencing / Acute Disease / Acute graft-versus-host disease / Adult / Alloreactivity / Biodiversity / Biomedical and Life Sciences / Biomedicine / Blood diseases / Child health / Children / DNA sequencing / Ecosystems / Fatty acids / Fecal microflora / Feces / Female / Gastrointestinal Microbiome / Gene Expression / Genes / Genetic research / Graft vs Host Disease - etiology / Graft vs Host Disease - microbiology / Graft-versus-host reaction / Gram-negative bacteria / Gut microbiota / Hematologic diseases / Hematologic Diseases - immunology / Hematologic Diseases - microbiology / Hematologic Diseases - therapy / Hematology / Hematopoietic stem cell transplantation / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic stem cells / Human Genetics / Humans / Inflammatory bowel disease / Intestinal microflora / Male / Microarrays / Microbiota / Microbiota (Symbiotic organisms) / Mortality / Patients / Pediatric patients / Pediatric research / Pediatrics / Phylogenetics / Phylogeny / Prognostics and diagnostics/biomarkers / Research Article / Risk factors / RNA / rRNA 16S / Stem cell transplantation / Stem cells / Studies / Surgery / Time Factors / Transplantation, Homologous - adverse effects / Transplants & implants