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

• Published in: Transplant immunology Vol. 78; p. 101836
• Main Authors: Yazdandoust, Ehsan, Hajifathali, Abbas, Roshandel, Elham, Zarif, Mahin Nikougoftar, Pourfathollah, Ali Akbar, Parkhideh, Sayeh, Mehdizadeh, Mahshid, Amini-Kafiabad, Sedigheh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2023
• Subjects: Acute graft-versus-host disease (aGVHD); Forkhead Transcription Factors; Gastrointestinal Microbiome; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Medicin och hälsovetenskap; Prebiotic; Probiotic; Probiotics - therapeutic use; Regulatory T cell; T-Lymphocytes, Regulatory; Probiotic; Acute graft-versus-host disease (aGVHD); Prebiotic; Hematopoietic stem cell transplantation; Regulatory T cell
• ISSN: 0966-3274; 1878-5492; 1878-5492
• DOI: 10.1016/j.trim.2023.101836

Acute 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. We 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. Within 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). Our 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. •Synbiotic intake in allo-HSCT patients leads to a reduction in the incidence and severity of acute GVHD.•Regulatory T cell in the patients who experience acute GVHD is significantly lower after HSCT.•Probiotics and prebiotics have beneficial effects on the patients undergoing allo-HSCT.