[Research Articles] Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation
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 producti...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Khuat, L. T., Le, C. T., Pai, C.-C. S., Shields-Cutler, R. R., Holtan, S. G., Rashidi, A., Parker, S. L., Knights, D., Luna, J. I., Dunai, C., Wang, Z., Sturgill, I. R., Stoffel, K. M., Merleev, A. A., More, S. K., Maverakis, E., Raybould, H. E., Chen, M. Tags: Research Articles Source Type: research
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