Keywords

GERD, Barrett's Esophagus, Esophageal Adenocarcinoma, Probiotics

Abstract

Chronic heartburn or gastroesophageal reflux disease (GERD) affects approximately 25% of the US population [1]. Repeated bile acid exposure from the regurgitation of stomach contents leads to the production of reactive oxygen species (ROS), which can cause oxidative DNA damage and promote genomic instability [2]. Barrett’s esophagus (BE), which can develop as a response to chronic bile acid exposure, increases the risk of esophageal adenocarcinoma (EAC) by 30% to 125% [1].

There are more than 18,000 new cases of esophageal cancer in the United States each year, and while its incidence is relatively low compared to other cancers, its mortality rate is disproportionately high [3]. Despite declining incidence for other cancers, EAC has shown a concerning increase over the past several decades [4]. Diagnosis methods include barium swallow, CT, PET, ultrasound, esophagoscopy, and bronchoscopy. Treatments typically consist of surgery, radiation, and chemotherapy, which are invasive and are often associated with lasting side effects.

Common resident bacteria in the healthy esophagus include Streptococcus spp. and probiotic Lactobacillus spp [5]. As the abundance of these commensal bacteria is reduced in GERD and BE, we hypothesize that reintroduction of these bacteria could prevent BE and EAC. We aim to test postbiotic metabolites, secreted by these commensals, for their antioxidant and anti-inflammatory function in-vitro.

Our previous research showed that live Lactobacilli spp. accelerated DNA damage repair in bile-exposed normal human esophageal cells. To determine whether secreted metabolites or host contact with live bacteria is required for this reduction, we exposed normal esophageal epithelial cells to two different types of bile, deoxycholic acid (DCA) and ox bile, to simulate the in-vivo conditions of GERD. Following bile injury, either live bacteria or bacterial growth media (conditioned media, CM) from L.acidophilus and S. gordonii were added. A comet assay showed a generalized reduction in DNA damage in cells with live bacterial or CM recovery periods. Immunofluorescence using antibodies against DNA damage markers (pH2AX and RAD51) and an inflammation marker (NF-kB) demonstrated a significant acceleration of DNA repair following CM exposure. Secretion of a pro-inflammatory cytokine, CXCL1, was reduced in the presence of CM comparable to live bacteria as determined using a Proteome Profiler array. Ongoing experiments focus on using CM fractions to identify post-metabolic factors that contribute to the prevention of BE.

Thesis Completion Year

2026

Thesis Completion Semester

Spring

Thesis Chair

Andl, Claudia

College

College of Medicine

Department

Biomedical Sciences

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

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