Esophageal Microbiome, Epithelial Gene Expression, and Response to Topical Swallowed Steroids in Pediatric Eosinophilic Esophagitis
小儿嗜酸粒细胞性食管炎的食管微生物群、上皮基因表达以及对局部吞咽类固醇的反应
基本信息
- 批准号:10558624
- 负责人:
- 金额:$ 21.63万
- 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:2022-02-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcinetobacterAddressAllergensBiopsyBiopsy SpecimenChildChildhoodClassificationClinicalCollagenControl GroupsCytokine SignalingDeglutitionDisease remissionDistalDistressDown-RegulationEcologyEndoscopyEnvironmental Risk FactorEosinophilic EsophagitisEpitheliumEsophageal StenosisEsophageal TissueEsophagusExtracellular MatrixFailure to ThriveFibrosisFoodFoundationsFunctional disorderFutureGene ExpressionGene Expression RegulationGenesGenetic TranscriptionHigh PrevalenceHistologicHomeostasisImpairmentIncidenceInflammatory ResponseKnowledgeMediatingMolecularMucous MembraneOperative Surgical ProceduresOutcomeOutcome StudyPathway interactionsPatientsPediatric cohortPeptide HydrolasesPlayPrevalencePropertyProtocols documentationQuality of lifeResearchRoleSamplingSteroid therapySteroidsStructureSymptomsTestingTimeTissue SampleTreatment EfficacyUp-RegulationVomitingbacterial communitycohortdisabling symptomeosinophileosinophilic inflammationfeedinghigh riskhost microbiomeimmune functionimprovedinsightmetagenomemetagenomic sequencingmetatranscriptomicsmicrobialmicrobial communitymicrobiomemicrobiome compositionmicrobiome signaturemicrobiotanovelpersonalized carepersonalized therapeuticpredicting responseresponserestorationtherapy outcometranscriptometreatment response
项目摘要
Summary
Eosinophilic esophagitis (EoE) is an increasingly prevalent allergen-mediated clinico-pathologic
condition. It is characterized by the presence of esophageal symptoms and impaired esophageal
epithelial barrier in the setting of eosinophilic inflammation. The children with EoE suffer from
debilitating symptoms such as vomiting, feeding difficulties, inability to swallow, and failure to thrive.
Topical swallowed steroids (TSS) are the mainstay of EoE therapy and can lead to improvement in
symptoms, histologic remission, and restoration of the epithelial barrier function. However, over 50% of
children with EoE may not respond to TSS and continue to suffer from unremitting symptoms which can
negatively impact their quality of life. Additionally, the uncontrolled eosinophilic inflammation can further
compromise the esophageal epithelial properties and lead to sub-epithelial fibrosis resulting in
esophageal stricture and esophageal food impactions requiring emergent endoscopy or surgical
intervention. To date, very little is known about the factors associated with response to TSS in children
with EoE. In particular, the role of esophageal microbiome and how it interacts with the esophageal
epithelium to impact the response to TSS in children with EoE has not been studied. It is important to
understand this relationship as the rapid increase in the incidence and prevalence of EoE strongly
indicates that environmental factors such as esophageal microbiome may have an essential role in
modulating the treatment response in EoE. The objective of this application is to investigate the role of
the esophageal microbiome and its cross-talk with the host epithelium in TSS responders (EoE-TSSr),
TSS non-responders (EoE-TSSnr) and non-EoE controls. For the first time, it would determine whether
TSS therapy outcomes are derived in part by resident esophagus microbiota structure and function that
can potentially alter esophageal barrier integrity and immune function. Using a pediatric cohort of EoE-
TSSr, EoE-TSSnr and non-EoE controls we will: a) characterize the microbiome composition and
functional capability at the species level in the esophagus tissue samples, b) determine the mechanistic
association between active esophagus microbiome, host epithelium expression profiles, and TSS
therapy efficacy. The outcomes of this study will expand our understanding about the factors
associated with response to TSS in pediatric EoE. In the long term, this study will lay the foundation for
personalizing the care in pediatric EoE.
摘要
嗜酸性食管炎(EoE)是一种日益流行的由变应原介导的临床病理
条件。它的特点是出现食道症状和食道受损。
上皮屏障在嗜酸性炎症中的作用。患有EoE的儿童患有
令人虚弱的症状,如呕吐、进食困难、吞咽困难和无法茁壮成长。
局部吞服类固醇(TSS)是EoE治疗的主要手段,可以改善
症状、组织学缓解和上皮屏障功能的恢复。然而,超过50%的
患有EoE的儿童可能对TSS没有反应,并继续遭受持续不断的症状,这可能
对他们的生活质量产生负面影响。此外,失控的嗜酸性炎症可进一步
损害食道上皮特性并导致亚上皮下纤维化
需要急诊内窥镜或外科手术的食道狭窄和食道食物嵌塞
干预。到目前为止,对儿童对TSS反应的相关因素知之甚少。
使用EoE。特别是,食道微生物组的作用以及它如何与食道相互作用
上皮细胞对EoE儿童TSS反应的影响尚未被研究。重要的是要
将这种关系理解为EoE发病率和流行率的快速增长
提示食道微生物群等环境因素可能在食道感染中起重要作用
调节EoE的治疗反应。此应用程序的目标是调查
TSS反应者的食道微生物组及其与宿主上皮的交互作用(EoE-TSSr),
TSS无响应器(EoE-TSSnr)和非EoE控制。这将是第一次决定是否
TSS治疗结果在一定程度上是由驻留的食道微生物区系结构和功能得出的
可能会改变食道屏障的完整性和免疫功能。使用EoE的儿科队列-
TSSR、EoE-TSSnr和非EoE对照我们将:a)表征微生物组组成和
食道组织样本在物种水平上的功能能力,b)决定机制
活跃的食道微生物群、宿主上皮细胞表达谱与TSS的关系
治疗效果。这项研究的结果将扩大我们对这些因素的理解
与儿童EoE对TSS的反应有关。从长远来看,这项研究将为
儿科急诊室的个性化护理。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Salivary immunoinflammatory proteins identify children with eosinophilic esophagitis.
唾液免疫炎症蛋白可识别患有嗜酸性粒细胞性食管炎的儿童。
- DOI:10.1111/all.16040
- 发表时间:2024
- 期刊:
- 影响因子:12.4
- 作者:Hiremath,Girish;Wang,Yu;Correa,Hernan;Sheng,Quanhu;Rajagopala,SeesandraV
- 通讯作者:Rajagopala,SeesandraV
{{
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 }}
Girish Hiremath其他文献
Girish Hiremath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('Girish Hiremath', 18)}}的其他基金
Esophageal Microbiome, Epithelial Gene Expression, and Response to Topical Swallowed Steroids in Pediatric Eosinophilic Esophagitis
小儿嗜酸粒细胞性食管炎的食管微生物群、上皮基因表达以及对局部吞咽类固醇的反应
- 批准号:
10432560 - 财政年份:2022
- 资助金额:
$ 21.63万 - 项目类别:
Precision Medicine Approaches for Eosinophilic Esophagitis Using Raman Spectroscopy and Machine Learning
利用拉曼光谱和机器学习治疗嗜酸性食管炎的精准医学方法
- 批准号:
10551207 - 财政年份:2022
- 资助金额:
$ 21.63万 - 项目类别:
Precision Medicine Approaches for Eosinophilic Esophagitis Using Raman Spectroscopy and Machine Learning
利用拉曼光谱和机器学习治疗嗜酸性食管炎的精准医学方法
- 批准号:
10350762 - 财政年份:2022
- 资助金额:
$ 21.63万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 21.63万 - 项目类别:
Research Grant