Gut microbiota (GM) composition has been correlated with the onset of acute graft-versus-host disease (aGvHD), however, 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).
Allogeneic HSCT (allo-HSCT) is a therapeutic option for many patients with high-risk hematopoietic malignancies and hematological disorders. However, the success of the procedure is often hindered by a process in which donor-derived T cells recognize host healthy tissue as non-self, causing an immune-mediated complication which are instrumental in determining ill health and mortality of patients. An association between aGvHD and the GM has long been hypothesized 2,3due to the ever-increasing evidence of the involvement of the GM in the regulation of the human immune system functionality. 4
Elena Biagi from the University of Bologna, Italy, and colleagues, published findings in the journal BMC Medical Genomics on a study exploring the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset. 1
Patients and methods
- N = 36 (male n = 20, female n = 16)
- Stools were collected at three-timepoints: before HSCT, at time of engraftment and > 30 days following HSCT
- Protocol was approved by the University of Bologna Ethics Committee(ref. number 19/2013/U/Tess)
- Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation
- Inclusion criterion was the availability of a pre-HSCT fecal sample and of at least two samples collected after HSCT
- 5 out of 36 patients received intravenous levofloxacin 5to the complete neutrophil recovery
- All patients observed complete fasting beginning from the onset of oral mucositis or diarrhea with the administration of parenteral nutrition until the day of engraftment
- Conditioning regimen: n = 32 patients received a myeloablative busulfan (or treosulfan)-based conditioning regimen, n = 3 patients received total body irradiation-based conditioning regimen, and n = 1 patient received a non-myeloablative preparative regimen with cyclophosphamide/fludarabine
- Antiviral and antifungal prophylaxis was administered from day −1 and +2 respectively
- Antibiotic empiric therapy, with piperacillin/tazobactam or ceftazidime, was given in case of neutropenic fever in 29/36 cases
- N = 7 cases received antibiotic therapy at the beginning of the neutropenic phase independently from the onset of fever, and n = 4 cases received a cephazolin/piperacillin tazobactam-based anti-streptococcal prophylaxis before the engraftment phase
Dr. Biagi and her team presented a longitudinal observation of microbiota dynamics in pediatric patients undergoing HSCT for a variety of hematological diseases. Despite the complexity of the study in terms of possible confounding variables (i.e. chemotherapy, antibiotics, proton-pump inhibitors, and hospitalization), it was possible to detect a signature of the future development of aGvHD in the GM composition before HSCT.
The researchers indicated that children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This assumed aGvHD predisposing ecosystem state was characterized by firstly a reduced diversity, and secondly, the team identified a lower Blautia content, as well as an increase in Fusobacterium abundance. Dr. Biagi and her team found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. The 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.