Foregut microbiome in development of esophageal adenocarcinoma

食管腺癌发生过程中的前肠微生物组

• 批准号: 8791776
• 负责人: Karen E. Nelson
• 金额: $ 103.33万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-24 至 2016-01-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8791776
• 关键词: Age; Anatomy; Antibiotics; Archaea; Barrett Esophagus; Biota; Case-Control Studies; DNA Viruses; Development; Disease; Disease Association; Disease Pathway; Disease Progression; Distal; Elderly; Endoscopy; Environmental Risk Factor; Esophageal; Esophageal Adenocarcinoma; Esophagitis; Esophagus; Female; Gastric Acid; Gastroesophageal reflux disease; Gender; Genes; Goals; Grouping; Heartburn; Histology; Hospitals; Incidence; Integration Host Factors; Intestinal Metaplasia; Link; Literature; Logistic Regressions; Metagenomics; Monitor; New York; Odds Ratio; Oral cavity; Patients; Peptic Esophagitis; Pharmaceutical Preparations; Phenotype; Pilot Projects; Population; Prevalence; Primitive foregut structure; Probiotics; Recombinant DNA; Recruitment Activity; Reflux; Research Design; Risk Factors; Sampling; Staging; Stomach; Symptoms; Teaching Hospitals; Technology; Testing; Universities; Veterans; Virus; age group; cancer type; design; disorder risk; fungus; male; medical schools; metagenome; microbial; microbiome; novel strategies; population survey; prebiotics; prevent; pyrosequencing; spatial relationship; treatment strategy; trend; upper GI series

Project Summary Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years, which can not be explained by the usual environmental or host factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett's esophagus (BE). Our preliminary study in elderly male veterans found two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will examine whether the finding in elderly male subjects also applies to younger as well as female subjects. We will conduct a case control study to demonstrate the microbiome- disease association in every stage of GERD sequence as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA.

项目摘要 食道腺癌（EA），与胃胃胃胃胃胃倒流有关的癌症类型 疾病（GERD）在过去30年中增加了6倍，这不能用通常的解释 环境或宿主因素。 EA是一系列与GERD相关疾病的最终结果，此前 反流食管炎（RE）和巴雷特的食管（BE）。我们在老年男性退伍军人的初步研究发现 食管中两种类型的微生物群。携带II型微生物群的患者> 15倍可能具有 食管炎，比携带I型微生物群的食管炎。在一项小型研究中，我们还发现3个 3例EA属于II型生物群。这些发现为理解 EA发病率最近激增。我们的长期目标是确定GERD序列的原因。这 要测试的假设是前述微生物组的变化与EA及其前体有关， RE并处于GERD序列。我们将检查老年男性受试者的发现是否也适用 既年轻和女性受试者。我们将进行案例控制研究，以证明微生物组 - GERD序列的每个阶段的疾病关联，并分析了变化的趋势 微生物组沿着疾病沿EA的进展，两个特定的目的。目标1是进行全面的 对前肢微生物组的人口调查，并证明了其与GERD序列的关联。 此外，食管微生物群和上游（口）和下游之间的空间关系 （胃）前体微生物群以及微生物组疾病关联的时间稳定性也将是 检查。 AIM 2是定义远端食管元基因组，并证明其与GERD的关联 顺序。详细的分析将包括途径疾病和基因 - 疾病酶关联。古细菌，真菌 病毒（如果鉴定出）也将与疾病相关。前肢之间的重要关联 微生物组和GERD序列（如果证明）将是最终测试是否是否 对于向EA的表型变化序列的发展需要异常的微生物组。如果EA 它的前体代表一种微生态疾病，治疗GERD的原因可能是可能的， 例如，通过使用抗生素，益生菌或益生元来使菌群归一化。因果关系 GERD的治疗可以防止其进展并扭转EA发生率增加的当前趋势。

项目成果

De novo large cell neuroendocrine carcinoma of the prostate, case report and literature review.

前列腺新发大细胞神经内分泌癌病例报告及文献复习。

• 发表时间: 2014
• 期刊: American journal of clinical and experimental urology
• 影响因子: 1.2
• 作者: Acosta-Gonzalez,Gabriel;Qin,Jia;Wieczorek,Rosemary;Melamed,Jonathan;Deng,Fang-Ming;Zhou,Ming;Makarov,Danil;Ye,Fei;Pei,Zhiheng;Pincus,MatthewR;Lee,Peng
• 通讯作者: Lee,Peng

Urethral adenocarcinoma associated with intestinal-type metaplasia, case report and literature review.

尿道腺癌伴肠型化生病例报告并文献复习。

• 发表时间: 2013
• 期刊: International journal of clinical and experimental pathology
• 影响因子: 1.4
• 作者: Hale,ChristopherS;Huang,Hongying;Melamed,Jonathan;Xu,Ruliang;Roberts,Larry;Wieczorek,Rosemary;Pei,Zhiheng;Lee,Peng
• 通讯作者: Lee,Peng