Control of GVHD by Probiotics with individual Commensal Bacteria

益生菌与单个共生细菌控制 GVHD

基本信息

  • 批准号:
    10434993
  • 负责人:
  • 金额:
    $ 62.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-05 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) can cure a variety of benign and malignant hematopoietic disorders, but graft-versus-host disease (GVHD) remains a significant cause of transplant- related mortality and morbidity. Involvement of the gastrointestinal (GI) tract in the pathogenesis of GVHD has been substantiated by the translation of pre-clinical and clinical studies. The intestinal microbiota consists of a community of diverse microbes that reside in the gut and are critical for the host development, homeostasis, and immune regulation. Emerging evidence suggests that perturbations in the microbiota diversity result in aberrant systemic immune responses as well as pathogen colonization and mucosal invasion, fostering the development of GVHD. A clear rationale exists for targeting the microbiota with the goal to benefit patients after allo-HCT. Several interventional strategies have been explored by means of antibiotics, diet and prebiotics, probiotics, microbial metabolites, and fecal microbial transplantation (FMT). However, the identification of optimal FMT donors and appropriate stool screening for immune compromised patients is of a considerable challenge. Identifying and applying one or more live microorganisms that are safe and effective in improving health of HCT patients are of high merit. In the preliminary studies, we observed that abundance of Barnesiella in gut microbiota was associated with the reduction of GVHD in mice after allo-HCT. Furthermore, administration of a single Barnesiella strain, Barnesiella intestinihominis (BI), was safe and effective in preventing both acute and chronic GVHD in preclinical murine models. Our preliminary studies provide initial support that Barnesiella may be a means of probiotics that could benefit to patients after allo- HCT in the clinic. In fact, BI has been shown to clear of intestinal vancomycin-resistance Enterococcus that positively associates with GVHD severity in patients after allo-HCT. In this proposal, we will extend our exciting preliminary studies by further pursuing two Specific Aims: 1) to define the mechanisms by which BI and its derived metabolites modulate GVHD through maintaining gut homeostasis; 2) to determine the mechanisms by which BI and its derived metabolites modulate GVH/GVL responses through regulating donor T cells. We expect to firmly validate Barnesiella as a safe and efficacious probiotic to prevent and treat GVHD without compromising the GVL effect. Furthermore, we expect to understand the cellular and molecular mechanisms by which Barnesiella regulates microbiota, adaptive immunity, and intestinal barrier functions. If the proposed studies are successfully executed as expected, we will provide a compelling rationale that Barnesiella probiotics can be a therapeutic approach that benefits to patients after allo-HCT.
摘要

项目成果

期刊论文数量(0)
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Xue-Zhong Yu其他文献

Xue-Zhong Yu的其他文献

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{{ truncateString('Xue-Zhong Yu', 18)}}的其他基金

Targeting PIM-2 Kinase for Improving Cancer Immunotherapy
靶向 PIM-2 激酶以改善癌症免疫治疗
  • 批准号:
    10364948
  • 财政年份:
    2022
  • 资助金额:
    $ 62.39万
  • 项目类别:
Targeting PIM-2 Kinase for Improving Cancer Immunotherapy
靶向 PIM-2 激酶以改善癌症免疫治疗
  • 批准号:
    10559633
  • 财政年份:
    2022
  • 资助金额:
    $ 62.39万
  • 项目类别:
ER stress pathways regulate T-cell allogeneic and anti-tumor responses
ER应激通路调节T细胞同种异体和抗肿瘤反应
  • 批准号:
    10430505
  • 财政年份:
    2022
  • 资助金额:
    $ 62.39万
  • 项目类别:
ER stress pathways regulate T-cell allogeneic and anti-tumor responses
ER应激通路调节T细胞同种异体和抗肿瘤反应
  • 批准号:
    10577856
  • 财政年份:
    2022
  • 资助金额:
    $ 62.39万
  • 项目类别:
Control of GVHD by Probiotics with individual Commensal Bacteria
益生菌与单个共生细菌控制 GVHD
  • 批准号:
    10617324
  • 财政年份:
    2022
  • 资助金额:
    $ 62.39万
  • 项目类别:
Targeting IRE-1a/XBP-1 Axis for Control of Chronic GVHD and Leukemia Relapse
靶向 IRE-1a/XBP-1 轴控制慢性 GVHD 和白血病复发
  • 批准号:
    10578550
  • 财政年份:
    2018
  • 资助金额:
    $ 62.39万
  • 项目类别:
Targeting IRE-1a/XBP-1 Axis for Control of Chronic GVHD and Leukemia Relapse
靶向 IRE-1a/XBP-1 轴控制慢性 GVHD 和白血病复发
  • 批准号:
    10179448
  • 财政年份:
    2018
  • 资助金额:
    $ 62.39万
  • 项目类别:
Separation of GVH and GVL Responses Using Alloreactive CD8 iTregs
使用同种异体反应性 CD8 iTreg 分离 GVH 和 GVL 反应
  • 批准号:
    9333524
  • 财政年份:
    2017
  • 资助金额:
    $ 62.39万
  • 项目类别:
Control of GVHD and Leukemia Relapse by Targeting Cell Metabolism
通过靶向细胞代谢控制 GVHD 和白血病复发
  • 批准号:
    8815578
  • 财政年份:
    2015
  • 资助金额:
    $ 62.39万
  • 项目类别:
MicroRNA Regulates Graft-versus-Host Disease
MicroRNA 调节移植物抗宿主病
  • 批准号:
    9206138
  • 财政年份:
    2015
  • 资助金额:
    $ 62.39万
  • 项目类别:

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