scholarly journals Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation

2020 ◽  
Vol 12 (571) ◽  
pp. eaay7713
Author(s):  
Lam T. Khuat ◽  
Catherine T. Le ◽  
Chien-Chun Steven Pai ◽  
Robin R. Shields-Cutler ◽  
Shernan G. Holtan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Gut Microbiota ◽  
Stem Cell Transplantation ◽  
Antibiotic Treatment ◽  
Graft Versus Host Disease ◽  
Cytokine Production ◽  
Prophylactic Antibiotic ◽  
Graft Versus Host ◽  
Endotoxin Translocation ◽  
Prophylactic Antibiotic Treatment

The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO). These animals exhibited increased gut permeability, endotoxin translocation across the gut, and radiation-induced gastrointestinal damage after allo-HSCT. After allo-HSCT, both male and female DIO mouse recipients showed increased proinflammatory cytokine production and expression of the GVHD marker ST2 (IL-33R) and MHC class II molecules; they also exhibited decreased survival associated with acute severe gut GVHD. This rapid-onset, obesity-associated gut GVHD depended on donor CD4+ T cells and occurred even with a minor MHC mismatch between donor and recipient animals. Retrospective analysis of clinical cohorts receiving allo-HSCT transplants from unrelated donors revealed that recipients with a high body mass index (BMI, >30) had reduced survival and higher serum ST2 concentrations compared with nonobese transplant recipients. Assessment of both DIO mice and allo-HSCT recipients with a high BMI revealed reduced gut microbiota diversity and decreased Clostridiaceae abundance. Prophylactic antibiotic treatment protected DIO mouse recipients from endotoxin translocation across the gut and increased inflammatory cytokine production, as well as gut pathology and mortality, but did not protect against later development of chronic skin GVHD. These results suggest that obesity-induced alterations of the gut microbiota may affect GVHD after allo-HSCT in DIO mice, which could be ameliorated by prophylactic antibiotic treatment.

IL-13 production by donor T cells is prognostic of acute graft-versus-host disease following unrelated donor stem cell transplantation

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 717-724 ◽  
Author(s):  
William J. Jordan ◽  
Paul A. Brookes ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Robert I. Lechler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cytokine Production ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Despite the success of human leukocyte antigen (HLA) typing in allogeneic stem cell transplantation (SCT) it is rare to find an unrelated donor that is perfectly matched, making identification of “permissive” mismatches of paramount importance. Here, we describe novel associations between donor T-cell cytokine production during donor-antipatient mixed lymphocyte reactions (MLRs) and acute graft-versus-host disease (aGVHD). The data reveal positive correlations between both Th1-type and Th2-type cytokine production and GVHD and the assay established could potentially represent a useful tool for identification of permissible unrelated SCT donors. Associations between interleukin 13 (IL-13) levels and aGVHD were by far the strongest predictor of a GVHD (P = .0002). All patients suffering severe (grade III) aGVHD following SCT had donors who produced very high pretransplantation IL-13 responses, while those developing little or no aGVHD (grades 0-I) produced no IL-13 at all. IL-13 levels were independent of all other cytokines measured as well as cytotoxic T-lymphocyte precursor (CTLp) frequencies. The cytokines IL-5, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) also predicted development of aGVHD (P < .05 for all 3), appearing to be coproduced in the assay and correlating with estimated CTLp frequencies. The data challenge the notion that aGVHD is purely a Th1-type cytokine-driven response, high-lighting a novel and highly significant link between the Th2-type cytokine IL-13 and aGVHD.

scholarly journals Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation

2020 ◽  
Vol 4 (19) ◽  
pp. 4607-4617
Author(s):  
Kota Yoshifuji ◽  
Kyoko Inamoto ◽  
Yuko Kiridoshi ◽  
Kozue Takeshita ◽  
Satoshi Sasajima ◽  
...  
Keyword(s):  
Stem Cell ◽  
Gut Microbiota ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Mucosal Damage ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, management of aGVHD is important for successful transplantation. Mucosal damage and alteration of the gut microbiota after allo-HSCT are key factors in the development of aGVHD. We conducted a prospective study to evaluate the ability of prebiotics, which can alleviate mucosal damage and manipulate the gut microbiota, to mitigate posttransplantation complications, including aGVHD. Resistant starch (RS) and a commercially available prebiotics mixture, GFO, were administered to allo-HSCT recipients from pretransplantation conditioning to day 28 after allo-HSCT. Prebiotic intake mitigated mucosal injury and reduced the incidence of all aGVHD grades combined and of aGVHD grades 2 to 4. The cumulative incidence of skin aGVHD was markedly decreased by prebiotics intake. Furthermore, the gut microbial diversity was well maintained and butyrate-producing bacterial population were preserved by prebiotics intake. In addition, the posttransplantation fecal butyrate concentration was maintained or increased more frequently in the prebiotics group. These observations indicate that prebiotic intake may be an effective strategy for preventing aGVHD in allo-HSCT, thereby improving treatment outcomes and the clinical utility of stem cell transplantation approaches. This study was registered on the University Hospital Medical Information Network (UMIN) clinical trials registry (https://www.umin.ac.jp/ctr/index.htm) as #UMIN000027563.

POSSIBILITIES OF USING RUXOLITINIB TO IMPROVE THE RESULTS OF allo-HSCT (LITERATURE REVIEW)

2019 ◽  
Vol 65 (3) ◽  
pp. 330-336
Author(s):  
Irina Gribkova ◽  
I. Ishmatova ◽  
Mariya Davydovskaya ◽  
K. Kokushkin
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Literature Review ◽  
Stem Cell Transplantation ◽  
Clinical Improvement ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Graft Versus Host

The aim of the study was to systematize and summarize the current available data on ruxolitinib use in patients with myelofibrosis (MF) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve its results. The review includes data from foreign and domestic articles found in the PubMed and elibrary.ru databases describing the results of the use of ruxolitinib in patients with MF prior to allo-HSCT, including clinical cases, original scientific studies and reviews. It is reported that ruxolitinib therapy is safe, reduces mortality in the early post-transplantation period, reduces the incidence of acute and chronic graft-versus-host disease, and decreases the frequency of relapses. Clinical improvement with ruxolitinib therapy prior to allo-HSCT can be considered a prognostically favorable factor.

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