The Oral Microbiome for the Detection of Barretts Esophagus
用于检测 Barretts 食管的口腔微生物组
基本信息
- 批准号:10647639
- 负责人:
- 金额:$ 39.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAntibioticsBacteriaBarrett EsophagusCase/Control StudiesCellsCessation of lifeCharacteristicsDeglutitionDetectionDevelopmentDevicesDiagnosisDiscriminationDysplasiaEarly treatmentEndoscopyEnrollmentEnterobacteriaceaeEsophageal AdenocarcinomaEsophageal TissueEsophagusGastroesophageal reflux diseaseGene ExpressionHelicobacter InfectionsHigh grade dysplasiaIncidenceLaboratoriesLesionLinkMalignant NeoplasmsMalignant neoplasm of esophagusMethodsMichiganModelingNeoplasmsOral cavityPatient MonitoringPatientsPerformancePopulationPreventionPrimary CarePrognosisProspective, cohort studyPublic HealthReproducibilityRiskRisk FactorsSalivaSalivarySamplingSensitivity and SpecificitySiteStreptococcusTechniquesTestingTimeTranslatingValidationVeillonellaclinical predictive modelclinical riskcohortcost effectivecost effective interventiondiagnostic toolgut microbiomehigh riskimprovedinfection ratemicrobiomemicrobiome analysismicrobiome signaturemigrationminimally invasivemortalitynoveloral microbiomeperformance testspredictive modelingpredictive toolsprimary care settingprospectiverisk prediction modelsaliva analysissaliva samplescreeningvalidation studies
项目摘要
PROJECT SUMMARY
The incidence of esophageal adenocarcinoma (EAC) has risen 10-fold over the past half century and continues
to have a dismal prognosis. Barrett’s esophagus (BE) is the precursor lesion to EAC, and patients diagnosed
with BE undergo surveillance and endoscopic therapy for early neoplasia. However, more than 90% of EAC
patients are never diagnosed with BE beforehand, and widespread upper endoscopy to identify patients with BE
is expensive and of questionable value. Thus, there is an urgent need to develop minimally-invasive methods of
BE screening that can be easily performed in the primary care setting to allow for efficient and cost-effective
interventions to decrease EAC mortality. The esophageal microbiome is heavily influenced by migration of
bacteria from the mouth via swallowed secretions. The esophageal microbiome is altered in gastroesophageal
reflux and BE, and these changes may therefore reflect changes in the oral microbiome, an easily accessible
sampling site. In fact, we have demonstrated that there are marked alterations to the oral microbiome in patients
with BE, and a model based on specific taxa can distinguish BE patients with high sensitivity and specificity. We
hypothesize that microbiome analysis of saliva can identify patients with BE with high accuracy, thus
representing a novel, non-invasive screening test to identify patients at risk for EAC. In the current proposal we
aim to validate our preliminary findings in a large endoscopic cohort. We propose to leverage a completed study
of patients undergoing a first upper endoscopy with associated saliva samples, as well as patients with suspected
early neoplasia (high grade dysplasia or early EAC). In Aim 1, we will determine whether the oral microbiome
identifies patients with BE. We hypothesize that a microbiome score based on a model containing relative
abundance of Lautropia, Streptococcus, and Enterobacteriaceae identifies patients with and without BE with
high accuracy. In Subaim 1a, we will determine whether the oral microbiome in combination with a clinical
prediction model (Michigan Barrett’s Esophagus pREdiction Tool; M-BERET) identifies patients with Barrett’s
esophagus. As external validation of an oral microbiome signature, we will perform a case-control study using
saliva collected as part of a nationwide, primary care-based BE screening study (Subaim 1b). In Aim 2, we will
assess whether an oral microbiome signature can identify patients with BE and early neoplasia. In Aim 3, we will
conduct a prospective cohort study of 250 patients with and without BE, and collect serial saliva samples to
determine whether repeated sampling of the oral microbiome improves identification of patients with BE. We will
also assess temporal stability of an oral microbiome signature for the diagnosis of BE. We propose a novel,
biologically-based non-endoscopic approach to change the paradigm for EAC prevention. We hope that this will
lead to development of a laboratory-based testing strategy that is highly acceptable to patients, is cost-effective,
and can be easily translated to the primary care setting.
项目总结
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Clustering of Esophageal Cancer: Differences by Histology.
食管癌的聚集:组织学差异。
- DOI:10.1053/j.gastro.2022.09.003
- 发表时间:2023
- 期刊:
- 影响因子:29.4
- 作者:Rubenstein,JoelH
- 通讯作者:Rubenstein,JoelH
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Julian Abrams其他文献
Julian Abrams的其他文献
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{{ truncateString('Julian Abrams', 18)}}的其他基金
The Role of Secondary Bile Acids in Gastro-Esophageal Neoplasia
次级胆汁酸在胃食管肿瘤中的作用
- 批准号:
10693227 - 财政年份:2022
- 资助金额:
$ 39.66万 - 项目类别:
The Role of Secondary Bile Acids in Gastro-Esophageal Neoplasia
次级胆汁酸在胃食管肿瘤中的作用
- 批准号:
10506039 - 财政年份:2022
- 资助金额:
$ 39.66万 - 项目类别:
The Role of the Microenvironment in Barrett's Esophagus
微环境在巴雷特食管中的作用
- 批准号:
10607819 - 财政年份:2022
- 资助金额:
$ 39.66万 - 项目类别:
The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma
微生物组和 Notch 信号传导在食管腺癌中的作用
- 批准号:
10322389 - 财政年份:2021
- 资助金额:
$ 39.66万 - 项目类别:
The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma
微生物组和 Notch 信号传导在食管腺癌中的作用
- 批准号:
10747759 - 财政年份:2021
- 资助金额:
$ 39.66万 - 项目类别:
The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma
微生物组和 Notch 信号传导在食管腺癌中的作用
- 批准号:
10524194 - 财政年份:2021
- 资助金额:
$ 39.66万 - 项目类别:
The Role of the Microbiome and Notch Signaling in Esophageal Adenocarcinoma
微生物组和 Notch 信号传导在食管腺癌中的作用
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10543870 - 财政年份:2021
- 资助金额:
$ 39.66万 - 项目类别:
The Role of the Metaplastic Microenvironment in Barrett's Esophagus
化生微环境在巴雷特食管中的作用
- 批准号:
10381174 - 财政年份:2021
- 资助金额:
$ 39.66万 - 项目类别:
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