ID
45269
Description
Principal Investigator: Zhiheng Pei, MD, PhD, NYU Langone Medical Center, New York, NY, USA MeSH: Esophageal Adenocarcinoma,Barrett's Esophagus,GERD https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000260 The distal esophagus is an important anatomical area where gastric acid reflux can cause reflux esophagitis (RE), Barrett's esophagus (BE) (intestinal metaplasia), and esophageal adenocarcinoma (EA). The incidence of EA has increased 6-fold in the U.S. since the 1970s, parallel to a significant increase in the prevalence of gastroesophageal reflux diseases (GERD). Although specific host factors might predispose one to disease risk, such a rapid increase in incidence must be predominantly environmental. The cause remains unknown. Our hypothesis is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in the GERD sequence. We will conduct a case control study to characterize the microbiome in every stage of the GERD sequence as well as analyze the trend in changes in the microbiome along disease progression toward EA. Specific Aim 1. To conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence, by a 16S rRNA gene survey. We will analyze samples of the foregut microbiome at three anatomic loci: mouth, distal esophagus, and gastric corpus. Changes of the microbiota in the distal esophagus will be correlated with the phenotypes. 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. Specific Aim 2. To define distal esophageal metagenome and demonstrate its association with GERD sequence, by shotgun metagenomic analysis. We will first classify samples of the metagenome into metagenotypes by between-sample k-mer distance and correlate the metagenotypes with the four phenotypes. Subsequent detailed analyses will include pathway-disease and gene-disease associations. DNA viruses and fungi, if identified, also will be correlated with the phenotypes. A significant association between the foregut microbiome composition and GERD sequence, if demonstrated, will be the first step for eventually testing the causal hypothesis that an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microbial ecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiome through use of antibiotics, probiotics, or prebiotics. Causative therapy for GERD could prevent its progression and reverse the current trend of increasing incidence of EA.
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Versions (2)
- 07/06/2022 07/06/2022 - Dr. Christian Niklas
- 12/10/2022 12/10/2022 - Adrian Schulz
Détendeur de droits
Zhiheng Pei, MD, PhD
Téléchargé le
12 octobre 2022
DOI
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Licence
Creative Commons BY 4.0
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dbGaP phs000260 Foregut Microbiome in Development of Esophageal Adenocarcinoma
This subject consent data table contains subject IDs and consent group information.
- StudyEvent: SEV1
- Eligibility Criteria
- This subject consent data table contains subject IDs and consent group information.
- This subject sample mapping data table includes a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- This subject phenotype data table includes collection of subject sociodemography (n=5 variables; country of birth, age at first visit, gender, race, hispanic origin), diagnosis and phenotype, specifically, whether subject is normal, has reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma.
- This sample attributes data table includes body site, analyte type, tumor status, visit number and date, and sequencing center.
Similar models
This subject consent data table contains subject IDs and consent group information.
- StudyEvent: SEV1
- Eligibility Criteria
- This subject consent data table contains subject IDs and consent group information.
- This subject sample mapping data table includes a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- This subject phenotype data table includes collection of subject sociodemography (n=5 variables; country of birth, age at first visit, gender, race, hispanic origin), diagnosis and phenotype, specifically, whether subject is normal, has reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma.
- This sample attributes data table includes body site, analyte type, tumor status, visit number and date, and sequencing center.