Program Official

Principal Investigator

Awardee Organization

Columbia University Health Sciences
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

The Oral Microbiome for the Detection of Barretts Esophagus

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.


  • Solfisburg QS, Baldini F, Baldwin-Hunter B, Austin GI, Lee HH, Park H, Freedberg DE, Lightdale CJ, Korem T, Abrams JA. The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2024 Mar 1;33(3):371-380. PMID: 38117184
  • Annavajhala MK, May M, Compres G, Freedberg DE, Graham R, Stump S, Que J, Korem T, Uhlemann AC, Abrams JA. Relationship of the Esophageal Microbiome and Tissue Gene Expression and Links to the Oral Microbiome: A Randomized Clinical Trial. Clinical and translational gastroenterology. 2020 Dec;11(12):e00235. PMID: 33512805
  • Solfisburg QS, Baldini F, Baldwin-Hunter BL, Lee HH, Park H, Freedberg DE, Lightdale CJ, Korem T, Abrams JA. The Salivary Microbiome and Predicted Metabolite Production are Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma. bioRxiv : the preprint server for biology. 2023 Jun 28. PMID: 37425673
  • Rubenstein JH. Gastroesophageal Reflux Disease Is Not a Great Screening Criterion: Time to Move on to Other Strategies for Controlling the Burden of Esophageal Adenocarcinoma. The American journal of gastroenterology. 2022 Nov 1;117(11):1759-1761. Epub 2022 Sep 26. PMID: 36327434
  • Rubenstein JH. Clustering of Esophageal Cancer: Differences by Histology. Gastroenterology. 2023 Feb;164(2):310. Epub 2022 Sep 5. PMID: 36067820
  • Weh KM, Howard CL, Zhang Y, Tripp BA, Clarke JL, Howell AB, Rubenstein JH, Abrams JA, Westerhoff M, Kresty LA. Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome. JCI insight. 2024 Feb 8;9. (6). PMID: 38329812
  • Kuo SZ, Dettmer K, Annavajhala MK, Chong DH, Uhlemann AC, Abrams JA, Oefner PJ, Freedberg DE. Associations between urinary 3-indoxyl sulfate, a gut microbiome-derived biomarker, and patient outcomes after intensive care unit admission. Journal of critical care. 2021 Jun;63:15-21. Epub 2021 Jan 21. PMID: 33549909
  • Miller EH, Annavajhala MK, Chong AM, Park H, Nobel YR, Soroush A, Blackett JW, Krigel A, Phipps MM, Freedberg DE, Zucker J, Sano ED, Uhlemann AC, Abrams JA. Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19. Microbiology spectrum. 2021 Oct 31;9(2):e0005521. Epub 2021 Oct 13. PMID: 34643448
  • Baldwin-Hunter BL, Knotts RM, Leeds SD, Rubenstein JH, Lightdale CJ, Abrams JA. Use of the Electronic Health Record to Target Patients for Non-endoscopic Barrett's Esophagus Screening. Digestive diseases and sciences. 2019 Dec;64(12):3463-3470. Epub 2019 Jul 4. PMID: 31273597
  • Rubenstein JH, Sawas T, Wani S, Eluri S, Singh S, Chandar AK, Perumpail RB, Inadomi JM, Thrift AP, Piscoya A, Sultan S, Singh S, Katzka D, Davitkov P. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia. Gastroenterology. 2024 Jun;166(6):1020-1055. PMID: 38763697
  • Rubenstein JH, Stachler MD. TSP-9: A Barrett's Esophagus Biomarker Better Than Pathologists? Gastroenterology. 2023 Nov;165(5):1106-1107. Epub 2023 Sep 1. PMID: 37659675
  • Kumar A, Rara M, Yu M, Wen KW, Grady WM, Chak A, Iyer PG, Rustgi AK, Wang TC, Rubenstein JH, Liu Y, Kresty L, Westerhoff M, Kwon RS, Wamsteker E, Wang T, Berry L, Canto MI, Shaheen NJ, Wang KK, Abrams JA, Stachler MD. Molecular analysis of persistent and recurrent Barrett's esophagus in the setting of endoscopic therapy. Clinical and translational gastroenterology. 2024 Jul 15. Epub 2024 Jul 15. PMID: 39007490

Clinical Trials

Study Name Clinical Trial ID
Longitudinal Oral Microbiome Sampling for BE NCT05133102