Keywords

probiotics, cancer, Barrett's Esophagus, GERD, DNA damage, inflammation

Abstract

The prevalence of esophageal cancer is often attributed to the progression of gastroesophageal reflux disease (GERD) to Barrett’s Esophagus (BE) and finally to esophageal adenocarcinoma (EAC). During GERD and BE, biles in the refluxate induce oxidative stress, DNA damage, and inflammation, leading to cancerous dysplasia. Additionally, the esophageal microbiome has been demonstrated to shift to gram-negative-dominant throughout this progression. Our previous studies demonstrated the viability of gram-positive probiotic commensal Lactobacillus acidophilus under in vitro GERD conditions and its anti-genotoxic effects on bile-exposed esophageal cells. To assess reflux-induced oxidative stress, DNA damage, and inflammation and the effects of Lactobacillus supplementation on subsequent recovery, we exposed two lines of BE cells to two biles mimicking GERD and treated them with live Lactobacillus or its postbiotic secretions (metabolites). Using 8-oxo-guanine as a marker for reactive oxygen species (ROS) generation, we show that the potent bile acid deoxycholic acid (DCA) induces the presence of ROS, but addition of the postbiotic metabolites of L. acidophilus subsequently lowers this oxidative stress. As measured by two DNA damage repair markers through immunofluorescence, the biles cause significant increases in DNA damage, but both Lactobacillus treatments significantly reduce this damage. Our next experiments demonstrated that both bile types also induce significant inflammation through the NF-kB pathway and that Lactobacillus supplementation significantly reduces inflammatory activation. Furthermore, Lactobacillus significantly aids low-grade dysplastic Barrett’s Esophagus cells in recovery towards normal growth patterns 120 hours after insult by bile. Finally, various fractions of the postbiotic metabolites may share their bioactive (antioxidant, anti-genotoxic, and anti-inflammatory) properties. These results may illuminate novel therapeutic targets that are secreted by Lactobacillus. This study aims to investigate the role of Lactobacillus acidophilus in the prevention of esophageal adenocarcinoma.

Thesis Completion Year

2025

Thesis Completion Semester

Spring

Thesis Chair

Andl, Claudia

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Molecular Biology and Microbiology

Language

English

Access Status

Campus Access

Length of Campus Access

1 year

Campus Location

Orlando (Main) Campus

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Rights Statement

In Copyright