The Oral Microbiome for the Detection of Barretts Esophagus

用于检测 Barretts 食管的口腔微生物组

• 批准号: 10647639
• 负责人: Julian Abrams
• 金额: $ 39.66万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10647639
• 关键词: 16S ribosomal RNA sequencing; Antibiotics; Bacteria; Barrett Esophagus; Case/Control Studies; Cells; Cessation of life; Characteristics; Deglutition; Detection; Development; Devices; Diagnosis; Discrimination; Dysplasia; Early treatment; Endoscopy; Enrollment; Enterobacteriaceae; Esophageal Adenocarcinoma; Esophageal Tissue; Esophagus; Gastroesophageal reflux disease; Gene Expression; Helicobacter Infections; High grade dysplasia; Incidence; Laboratories; Lesion; Link; Malignant Neoplasms; Malignant neoplasm of esophagus; Methods; Michigan; Modeling; Neoplasms; Oral cavity; Patient Monitoring; Patients; Performance; Population; Prevention; Primary Care; Prognosis; Prospective, cohort study; Public Health; Reproducibility; Risk; Risk Factors; Saliva; Salivary; Sampling; Sensitivity and Specificity; Site; Streptococcus; Techniques; Testing; Time; Translating; Validation; Veillonella; clinical predictive model; clinical risk; cohort; cost effective; cost effective intervention; diagnostic tool; gut microbiome; high risk; improved; infection rate; microbiome; microbiome analysis; microbiome signature; migration; minimally invasive; mortality; novel; oral microbiome; performance tests; predictive modeling; predictive tools; primary care setting; prospective; risk prediction model; saliva analysis; saliva sample; screening; validation studies

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.

项目概要 食管腺癌 (EAC) 的发病率在过去半个世纪中上升了 10 倍，并且持续上升 巴雷特食管 (BE) 是 EAC 的先兆病变，且患者被诊断为预后不良。 患有 BE 的患者会接受早期肿瘤的监测和内镜治疗，然而，超过 90% 的 EAC 患者会接受早期肿瘤形成的监测和内镜治疗。 患者事先从未被诊断出患有 BE，并且广泛使用上消化道内窥镜检查来识别 BE 患者 昂贵且价值值得怀疑，因此，迫切需要微创的侵入性方法。 BE 筛查可以在初级保健机构中轻松进行，从而实现高效且经济高效的筛查 降低 EAC 死亡率的干预措施 食道微生物群很大程度上受到食道微生物迁移的影响。 通过吞咽分泌物从口腔中排出细菌 胃食管中的食管微生物群发生改变。 因此，这些变化可能反映了口腔微生物组的变化，这是一个容易获得的 事实上，我们已经证明患者的口腔微生物组发生了显着改变。 与BE，基于特定分类群的模型可以以高敏感性和特异性区分BE患者。 唾液微生物组分析可以高精度识别 BE 患者，因此 代表一种新颖的非侵入性筛查测试，用于识别有 EAC 风险的患者。 目的是在大型内窥镜队列中验证我们的初步结果，我们建议利用已完成的研究。 接受首次上消化道内窥镜检查和相关唾液样本的患者以及疑似患有 早期肿瘤（高度不典型增生或早期 EAC） 在目标 1 中，我们将确定口腔微生物组是否存在。 我们努力基于包含相关模型的微生物组评分来识别 BE 患者。 Lautropia、链球菌和肠杆菌科细菌的丰度可识别患有或不患有 BE 的患者 在 Subaim 1a 中，我们将结合临床来确定口腔微生物组。 预测模型（密歇根巴雷特食管预测工具；M-BERET）可识别巴雷特食管患者 作为口腔微生物特征的外部验证，我们将使用食道进行病例对照研究。 作为全国性初级保健 BE 筛查研究 (Subaim 1b) 的一部分，我们将收集唾液。 评估口腔微生物特征是否可以识别 BE 和早期肿瘤患者。在目标 3 中，我们将进行评估。 对 250 名患有和不患有 BE 的患者进行前瞻性队列研究，并收集系列唾液样本 确定口腔微生物组的重复采样是否可以改善 BE 患者的识别。 我们还评估了用于诊断 BE 的口腔微生物组特征的时间稳定性。 基于生物学的非内窥镜方法将改变 EAC 预防的范式。 导致开发出一种患者高度接受的基于实验室的检测策略，具有成本效益， 并且可以很容易地转化为初级保健环境。

项目成果

Use of the Electronic Health Record to Target Patients for Non-endoscopic Barrett's Esophagus Screening.

使用电子健康记录来针对患者进行非内窥镜巴雷特食管筛查。

• 发表时间: 2019-12
• 影响因子: 3.1
• 作者: Baldwin;Knotts, Rita M;Leeds, Samantha D;Rubenstein, Joel H;Lightdale, Charles J;Abrams, Julian A
• 通讯作者: Abrams, Julian A

The Salivary Microbiome and Predicted Metabolite Production are Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.

唾液微生物组和预测的代谢物产生与巴雷特食管到食管腺癌的进展相关。

• 发表时间: 2023-06-28
• 作者: Solfisburg, Quinn S;Baldini, Federico;Baldwin;Lee, Harry H;Park, Heekuk;Freedberg, Daniel E;Lightdale, Charles J;Korem, Tal;Abrams, Julian A
• 通讯作者: Abrams, Julian A

Clustering of Esophageal Cancer: Differences by Histology.

食管癌的聚集：组织学差异。

• 发表时间: 2023-02
• 影响因子: 29.4
• 作者: Rubenstein; Joel H
• 通讯作者: Joel H

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

唾液微生物组和预测的代谢物产生与巴雷特食管和高度不典型增生或腺癌有关。

• 发表时间: 2024-03-01
• 作者: Solfisburg, Quinn S;Baldini, Federico;Baldwin;Austin, George I;Lee, Harry H;Park, Heekuk;Freedberg, Daniel E;Lightdale, Charles J;Korem, Tal;Abrams, Julian A
• 通讯作者: Abrams, Julian A