High stearic acid diet modulates gut microbiota and aggravates acute graft-versus-host disease.
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ABSTRACT:
SUBMITTER: Yang B
PROVIDER: S-EPMC8298483 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Allogeneic hematopoietic stem cell transplantation is one of the most effective treatment strategies for leukemia, lymphoma, and other hematologic malignancies. However, graft-versus-host disease (GVHD) can significantly reduce the survival rate and quality of life of patients after transplantation, and is therefore the greatest obstacle to transplantation. The recent development of new technologies, including high-throughput sequencing, metabolomics, and others, has facilitated great progress in understanding the complex interactions between gut microbiota, microbiota-derived metabolites, and the host. Of these interactions, the relationship between gut microbiota, microbial-associated metabolites, and GVHD has been most intensively researched. Studies have shown that GVHD patients often suffer from gut microbiota dysbiosis, which mainly manifests as decreased microbial diversity and changes in microbial composition and microbiota-derived metabolites, both of which are significant predictors of poor prognosis in GVHD patients. Therefore, the purpose of this review is to summarize what is known regarding changes in gut microbiota and microbiota-derived metabolites in GVHD, their relationship to GVHD prognosis, and corresponding clinical strategies designed to prevent microbial dysregulation and facilitate treatment of GVHD.
| S-EPMC10905340 | biostudies-literature
Project description:AimThe gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD.MethodsFecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition.ResultsFrom the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α.ConclusionsDynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.
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| S-EPMC10653043 | biostudies-literature
Project description:We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal. In multivariable analysis of data from 613 allogeneic haematopoietic cell transplant recipients, peri-engraftment presence of O. splanchnicus was associated with ~50% lower risk for grade II-IV aGVHD (hazard ratio 0·53, 95% confidence interval 0·28-1·00, P = 0·05). O. splanchnicus may protect rs4415345G individuals against aGVHD.
| S-EPMC7536617 | biostudies-literature
Project description:Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.
| S-EPMC6240460 | biostudies-other
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| S-EPMC6258918 | biostudies-literature
Project description: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.
| S-EPMC8525601 | biostudies-literature
Project description: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.
| S-EPMC7556149 | biostudies-literature
Project description:Although studies have reported that intestinal microbiota are associated with acute graft-versus-host disease (aGVHD), they lacked a satisfactory method for predicting aGVHD. We collected stool and blood samples at day 15 posttransplant from 150 patients from two centers who underwent myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT). Stool microbiota were detected by 16S ribosomal RNA gene sequencing; inflammatory factors and T lymphocytes were detected by multiplex immunoassays and flow cytometry, respectively. A gut microbiota score (GMS) from a LASSO (least absolute shrinkage and selection operator) model was developed and validated to predict aGVHD. In the discovery cohort, the GMS could predict II-IV aGVHD (area under the receiver operating characteristic [ROC] curve [AUC] = 0.904, P < .0001). Furthermore, the validation model was consistent with the discovery set (AUC = 0.887, P < .0001). Regulatory T/T-helper 17 (Treg/Th17) cells ratio in the low GMS subgroup was higher compared with the high GMS (P = .012), and the validation set is consistent with the discovery set (P = .003). In addition, high cytokine levels were associated with high GMS. In conclusion, the GMS at neutrophil engraftment could predict aGVHD, and it was a potential and novel method. The GMS was associated with the inflammatory factor and Treg/Th17 balance.
| S-EPMC7154648 | biostudies-literature
Project description:The growing understanding of the bidirectional relationship between the gastrointestinal (GI) microbiome and the immune system has opened up new avenues for treatment of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) is the transfer of stool from a donor to a recipient who harbors a perturbed GI microbiome resulting in disease. We review the rationale for performing FMT for the treatment of acute GVHD, and summarize data on the safety and efficacy of the procedure among allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Overall, FMT is a promising strategy in treating and preventing HSCT-related complications. However, caution should be exerted as HSCT recipients are highly immunosuppressed and unanticipated infectious adverse events may appear with the increasing application of FMT.
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