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

被引:12
作者
Yazdandoust, Ehsan [1 ]
Hajifathali, Abbas [2 ]
Roshandel, Elham [2 ]
Zarif, Mahin Nikougoftar [3 ]
Pourfathollah, Ali Akbar [4 ]
Parkhideh, Sayeh [2 ]
Mehdizadeh, Mahshid [2 ]
Amini-Kafiabad, Sedigheh [1 ]
机构
[1] High Inst Res & Educ Transfus Med, Blood Transfus Res Ctr, Tehran, Iran
[2] Shahid Beheshti Univ Med Sci, Hematopoiet Stem Cell Res Ctr, Tehran, Iran
[3] Karolinska Univ, Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med,Hosp Huddinge, Stockholm, Sweden
[4] Tarbiat Modares Univ, Fac Med Sci, Dept Immunol, Tehran, Iran
基金
美国国家科学基金会;
关键词
Hematopoietic stem cell transplantation; Acute graft -versus -host disease (aGVHD); Regulatory T cell; Prebiotic; Probiotic; VERSUS-HOST-DISEASE; INTESTINAL MICROBIOTA; METABOLITES;
D O I
10.1016/j.trim.2023.101836
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: 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.Methods/Study Design: 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.Results: Within first 100 days of observation, the incidence of severe (grade III/IV) aGVHD in the a synbiotictherapy 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 symbiotictreated patients than in the control group (75%), but the difference was not statistically significant (P = 0.234).Conclusion: 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.
引用
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页数:7
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