Gut microbiota intervention by pre and probiotics can induce regulatory T cells and reduce the risk of severe acute GVHD following allogeneic hematopoietic stem cell transplantation |
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| Affiliation: | 1. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran;2. Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. Center for Hematology and Regenerative Medicine, Karolinska Institutet, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden;4. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;1. Johns Hopkins University School of Medicine, Baltimore, MD, USA;2. Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA;3. Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA;4. Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, GA, USA;1. Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People''s Hospital, Wuxi 214023, China;2. Department of Lung Transplant, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China;1. Clinical Hospital, Kidney Transplant Unit, Belo Horizonte, MG, Brazil;2. Faculty of the Hospital Santa Casa, Belo Horizonte, MG, Brazil;3. IMUNOLAB – Laboratory of Transplant Immunology, Belo Horizonte, MG, Brazil;4. Faculty of Medical Sciences of Minas Gerais, Belo Horizonte, MG, Brazil;5. Clinical Hospital of Porto Alegre, Rio Grande do Sul, Brazil;6. Mater Dei Hospital Minas Gerais, Belo Horizonte, MG, Brazil;7. Biocor Hospital, Belo Horizonte, Minas Gerais, Brazil;1. Barcelona Tissue Bank, Banc de Sang i Teixits (BST), Barcelona, Spain;2. Arthroscopy Unit, Department of Orthopaedics, Hospital Clinic de Barcelona, Barcelona, Spain;3. Biomedical Research Institute (IIB-Sant Pau; SGR1113), Barcelona, Spain;4. Vall d''Hebron Institute of Research (VHIR), Barcelona, Spain |
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| Abstract: | BackgroundAcute graft-versus-host disease (aGVHD) is one of the leading causes of limitation and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous studies have shown that changes in the gut microbiome diversity increased post-transplant problems, including the occurrence of aGVHD. Probiotics and prebiotics can reconstitute the gut microbiota and thus increase bacterial metabolites such as short-chain fatty acids (SCFAs) that have immunomodulatory effects preventing aGVHD in recipients of allo-HSCTs.Methods/Study DesignWe conducted a pilot randomized clinical trial to investigate whether oral synbiotics are associated with the prevention or reduction in occurrence/severity and mitigate complications of aGVHD following allo-HSCT. A commercially available synbiotic mixture containing high levels of 7 safe bacterial strains plus fructo-oligosaccharides as a prebiotic was administered to allo-HSCT recipients. Out of 40 allo-HSCT patients, 20 received daily a synbiotic 21 days prior to transplantation (days ?21 to day 0). In contrast, in the control group 20 recipients of allo-HSCT did not receive a symbiotic therapy.ResultsWithin first 100 days of observation, the incidence of severe (grade III/IV) aGVHD in the a synbiotic-therapy group was 0% (0 out of 20 patients), whereas it was 25% (5 out of 20 patients) in the control group (P = 0.047). The median percentage of CD4 + CD25 + Foxp3+ regulatory T cells (Tregs) among CD4+ lymphocytes on day 28 after HSCT in the synbiotic group was higher (2.54%) than in control group (1.73%; P = 0.01). There was no difference in Treg cells on day 7 after HSCT between two groups. However, the median percentage and the absolute count of Tregs in patients who experience aGVHD was significantly lower on days 7 and 28 after HSCT (both P < 0.05). The overall 12-month survival (OS) rate was higher (90%) in the symbiotic-treated patients than in the control group (75%), but the difference was not statistically significant (P = 0.234).ConclusionOur preliminary findings suggest that synbiotic intake before and during the conditioning regimen of allo-HSCT patients may lead to a reduction in the incidence and severity of aGVHD through the induction of CD4 + CD25 + Foxp3+ regulatory T cells, thus contributing to the improvement of transplant outcomes. Much larger studies are needed to confirm our observations. |
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