The Gut Microbiota and Graft versus Host Disease (GVHD)

肠道微生物群和移植物抗宿主病 (GVHD)

基本信息

项目摘要

Abstract: The Gut Microbiota and Graft-versus-Host Disease Hematopoietic cell transplantation (HCT) can be lifesaving for the treatment of numerous conditions, including leukemia, lymphoma, aplastic anemia, multiple myeloma, some immunodeficiencies, and other diseases. Unfortunately, graft-versus-host disease (GVHD) is a common complication of HCT, affecting up to 50% of allogeneic transplant recipients, despite human leukocyte antigen (HLA) matching between donor and recipient and despite use of immunoprophylaxis. GVHD most commonly affects the gut, liver, and skin, producing diarrhea, liver inflammation, and rashes, with varying stages (degrees) of organ involvement in different patients. GVHD is thought to arise from immune cells (e.g. T cells) in the graft that recognize host tissues as foreign and propagate an inflammatory response. It is unclear why some HCT recipients with equivalent HLA matching develop GVHD while others are spared, and why some patients with GVHD respond to immune suppression with glucocorticoid treatment while others develop steroid-refractory GVHD with high mortality. Some murine studies of bone marrow transplantation have shown that germ-free animals are protected from GHVD, and human studies have suggested that patients with GVHD have a less diverse gut microbiota early after transplant, pointing to the important role that microbes play in GVHD. This study will investigate which gut bacterial species or communities are most associated with risk of GVHD in a longitudinal study of HCT recipients where stool samples are collected weekly for 100 days, then monthly for 9 months, and subjected to broad-range 16S rRNA gene PCR with high-throughput sequencing for species-level taxonomic identification of bacteria. Stool samples from these patients will also be assayed for small molecule metabolites produced by the bacteria-host interaction that may mediate GVHD, such as short chain fatty acids and bile salts. The goal of this aim is to identify potential chemical effectors of GVHD. Metagenomic sequencing of stool DNA will be used to assess the functional and metabolic capability of gut bacterial communities to illuminate how particular bacterial communities produce metabolites linked to GVHD risk, and to identify particular bacterial species or strains with the metabolic machinery for impacting GVHD risk. Knowledge gained from this study could be used in the future to design interventions to reduce the risk of GVHD based on targeted manipulation of the gut microbiota. For example, identification of particular bacterial species or strains linked to protection from GVHD, and to the production of metabolites that mediate this protection, could lead to the development of probiotics or engineered bacterial communities for reducing GVHD risk or treating GVHD. Alternatively, enhancing the production of beneficial metabolites through exogenous administration or use of prebiotics, and blocking the production of harmful metabolites could emerge as another approach for mitigating GVHD without further immune suppression in these very compromised patients.
翻译后摘要:肠道菌群和移植物抗宿主病 造血细胞移植(HCT)可以挽救生命的治疗许多条件,包括 白血病、淋巴瘤、再生障碍性贫血、多发性骨髓瘤、某些免疫缺陷和其他疾病。 不幸的是,移植物抗宿主病(GVHD)是HCT的常见并发症,影响高达50%的 异基因移植受者,尽管供体和受者之间的人类白细胞抗原(HLA)匹配 尽管使用了免疫预防。GVHD最常影响肠道、肝脏和皮肤, 腹泻,肝脏炎症和皮疹,不同阶段(程度)的器官参与不同 患者GVHD被认为是由移植物中的免疫细胞(例如T细胞)引起的,所述免疫细胞将宿主组织识别为 并传播炎症反应。目前尚不清楚为什么一些具有等同HLA的HCT受者 匹配发展GVHD,而其他人则幸免,以及为什么一些GVHD患者对免疫应答 糖皮质激素治疗的抑制,而另一些发展为具有高死亡率的类固醇难治性GVHD。 一些小鼠骨髓移植的研究表明,无菌动物可以免受 GVHD和人类研究表明,GVHD患者早期肠道微生物群的多样性较低, 这表明微生物在GVHD中起着重要作用。这项研究将调查哪些肠道 在HCT的纵向研究中,细菌种类或群落与GVHD的风险最相关 接受者每周收集粪便样品,持续100天,然后每月收集,持续9个月,并进行 16 S rRNA基因大范围PCR结合高通量测序用于种级分类鉴定 细菌的。还将测定这些患者的粪便样品中的小分子代谢物, 可能介导GVHD的细菌-宿主相互作用,如短链脂肪酸和胆汁盐。的目标 目的是鉴定GVHD的潜在化学效应物。将使用粪便DNA的宏基因组测序 评估肠道细菌群落的功能和代谢能力, 细菌群落产生与GVHD风险相关的代谢物,并鉴定特定的细菌物种或 菌株与影响GVHD风险的代谢机制。从这项研究中获得的知识可能是 将来用于设计干预措施,以减少基于肠道靶向操作的GVHD风险 微生物群例如,鉴定与防止GVHD相关的特定细菌物种或菌株, 以及介导这种保护的代谢产物的产生,可能导致益生菌的发展, 用于降低GVHD风险或治疗GVHD的工程化细菌群落。或者,增强 通过外源性施用或使用益生元产生有益的代谢物,并阻断 有害代谢物的产生可能成为减轻GVHD的另一种方法,而无需进一步的 免疫抑制在这些非常脆弱的病人。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

DAVID Neal FREDRICKS其他文献

DAVID Neal FREDRICKS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('DAVID Neal FREDRICKS', 18)}}的其他基金

Fecal Microbiota Transplantation and Fiber for the Treatment of Graft-versus-host Disease After Hematopoietic Cell Transplantation
粪便微生物群移植和纤维治疗造血细胞移植后移植物抗宿主病
  • 批准号:
    10737446
  • 财政年份:
    2023
  • 资助金额:
    $ 23.18万
  • 项目类别:
ANAEROBE 2022: the 16th Biennial Congress of the Anaerobe Society of the Americas (ASA)
厌氧菌 2022:第 16 届美洲厌氧菌协会 (ASA) 双年度大会
  • 批准号:
    10464618
  • 财政年份:
    2022
  • 资助金额:
    $ 23.18万
  • 项目类别:
Prospective Epidemiologic Study of Novel Etiologic Agents of Pelvic Inflammatory Disease
盆腔炎新病因的前瞻性流行病学研究
  • 批准号:
    10668432
  • 财政年份:
    2020
  • 资助金额:
    $ 23.18万
  • 项目类别:
Prospective Epidemiologic Study of Novel Etiologic Agents of Pelvic Inflammatory Disease
盆腔炎新病因的前瞻性流行病学研究
  • 批准号:
    10220681
  • 财政年份:
    2020
  • 资助金额:
    $ 23.18万
  • 项目类别:
Prospective Epidemiologic Study of Novel Etiologic Agents of Pelvic Inflammatory Disease
盆腔炎新病因的前瞻性流行病学研究
  • 批准号:
    10471222
  • 财政年份:
    2020
  • 资助金额:
    $ 23.18万
  • 项目类别:
The Gut Microbiota and Graft versus Host Disease (GVHD)
肠道微生物群和移植物抗宿主病 (GVHD)
  • 批准号:
    10593458
  • 财政年份:
    2017
  • 资助金额:
    $ 23.18万
  • 项目类别:
The Gut Microbiota and Graft versus Host Disease (GVHD)
肠道微生物群和移植物抗宿主病 (GVHD)
  • 批准号:
    10053303
  • 财政年份:
    2017
  • 资助金额:
    $ 23.18万
  • 项目类别:
Male urethritis: Novel etiologies and natural history
男性尿道炎:新的病因和自然史
  • 批准号:
    8672151
  • 财政年份:
    2014
  • 资助金额:
    $ 23.18万
  • 项目类别:
Male urethritis: Novel etiologies and natural history
男性尿道炎:新的病因和自然史
  • 批准号:
    9001246
  • 财政年份:
    2014
  • 资助金额:
    $ 23.18万
  • 项目类别:
Male urethritis: Novel etiologies and natural history
男性尿道炎:新的病因和自然史
  • 批准号:
    8815259
  • 财政年份:
    2014
  • 资助金额:
    $ 23.18万
  • 项目类别:

相似海外基金

HLA-homozygous iPSC-cardiomyocytE Aggregate manufacturing technoLogies for allogenic cell therapy to the heart (HEAL)
HLA-纯合 iPSC-心肌细胞 用于心脏同种异体细胞治疗 (HEAL) 的聚集体制造技术
  • 批准号:
    10039902
  • 财政年份:
    2022
  • 资助金额:
    $ 23.18万
  • 项目类别:
    EU-Funded
Evaluation of the efficacy of LAT1 inhibitor to tumor stroma and immunity in an allogenic mouse model of colon cancer having abundant stroma.
在具有丰富基质的同种异体结肠癌小鼠模型中评估 LAT1 抑制剂对肿瘤基质和免疫的功效。
  • 批准号:
    21K15925
  • 财政年份:
    2021
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Mechanism of kidney injury associated with graft-versus-host disease after allogenic stem cell transplantation
同种异体干细胞移植后移植物抗宿主病相关肾损伤的机制
  • 批准号:
    21K08410
  • 财政年份:
    2021
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Clarification of the origin and maintenance mechanisms of junctional epithelium and identification of its stem cells using allogenic tooth germ transplantation
阐明交界上皮的起源和维持机制并利用同种异体牙胚移植鉴定其干细胞
  • 批准号:
    20K21672
  • 财政年份:
    2020
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
The study about the allogenic MSCs transplantation to the cardiac disease models.
同种异体间充质干细胞移植至心脏病模型的研究。
  • 批准号:
    18K16395
  • 财政年份:
    2018
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Artificial nerves containing allogenic basal lamellae scaffold and bone marrow derived stem cells
含有同种异体基底板层支架和骨髓干细胞的人工神经
  • 批准号:
    17K10951
  • 财政年份:
    2017
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Role of HSP90-alpha in preserving immunoprivilege of allogenic mesenchymal stem cells in the ischemic heart
HSP90-α 在保护缺血心脏同种异体间充质干细胞免疫特权中的作用
  • 批准号:
    370541
  • 财政年份:
    2017
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Operating Grants
Attempt to Prefabricate Vascularized Allogenic Bone in Recipient -Use of Cultured Bone Marrow Cells-
尝试在受者体内预制血管化的同种异体骨 - 使用培养的骨髓细胞 -
  • 批准号:
    16K10863
  • 财政年份:
    2016
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Allogenic micobiota-reconstitution (AMR) for the treatment of patients with diarhea-predominant irritable bowel syndrome (IBS-D) - the AMIRA trial
同种异体微生物群重建 (AMR) 用于治疗腹泻型肠易激综合征 (IBS-D) 患者 - AMIRA 试验
  • 批准号:
    276706135
  • 财政年份:
    2015
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Clinical Trials
Induction of thyme epithelial cells from iPS cells and application to allogenic transplantation
iPS细胞诱导百里香上皮细胞及其在同种异体移植中的应用
  • 批准号:
    15H04915
  • 财政年份:
    2015
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了