Abstract
BackgroundThe 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.MethodsThirty-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.ResultsChildren 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.ConclusionsWe 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.
Highlights
The onset of acute Graft-versus-Host Disease has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients
Some of the studies characterizing the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT) showed that a specific gut microbial population, the so-called “anti-inflammatory Clostridia”, i.e. members of the families Clostridiaceae, Lachnospiraceae, Ruminococcaceae and Eubacteriaceae, might be involved in the mechanism by which gut microbes exert a counteracting effect on acute Graft-versus-Host Disease (aGvHD) onset and progression [8,9,10]
Mentioned taxa were not excluded from subsequent analysis, but caution was taken in associating them with other variables, because of their possible relation to the different sequencing techniques used in the two studies (Roche 454 pyrosequencing of the 16S rRNA gene V4 hypervariable region in the 2015 study, and Illumina sequencing of the 16S rRNA gene V3-V4 hypervariable regions in the present study)
Summary
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. Mostly performed in small cohorts, have documented that aGvHD is associated with detectable shifts in the composition of the GM, in both murine and human (adult and child) HSCT recipients [6,7,8]. This finding supports the hypothesis that GM-derived metabolites (e.g. short-chain fatty acids (SCFAs)) and/or signaling molecules (e.g. microbe-associated molecular patterns (MAMPs)) can influence the onset of aGvHD. A partial confirmation of this observation has been provided by a study on a larger cohort of adults, in which the relative abundance of the Lachnospiraceae genus Blautia was correlated with reduced mortality from aGvHD [11]
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