Early signature of aGvHD development in the gut microbiota composition of pediatric patients given allogeneic hematopoietic cell transplantation for hematological disorders

A correlation between acute Graft-versus-Host Disease (aGvHD) and gut microbiota (GM) composition has been hypothesized, but experimental observations are still few and involve only small cohorts of patients, particularly in children. 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. In the present work, 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 phylogentetic structure were reconstructed by the16S rRNA gene sequencing.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 relative abundance. At time of engraftment, the GM resulted deeply affected 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 to HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.