Abstract 4233: The anti-genotoxic function of Lactobacillus species in the context of bile-mediated DNA damage and inflammation in experimental models of GERD

Abstract

Abstract Lactobacillus species are commensal organisms with probiotic characteristics found in the human oral cavity and gastrointestinal tract. It has been shown that gram-positive organisms, including lactobacilli, make up the majority of the microbiome in the healthy human esophagus. The general consensus is that the microbiome shifts from gram-positive to gram-negative bacteria during gastroesophageal reflux disease (GERD). In patients suffering from GERD, the esophageal tissue is injured by the low pH and bile acids present in the refluxate, resulting in Barrett’s esophagus if untreated. Interestingly, it has been reported that there is a proportional increase in gram-positive lactobacilli within the esophagus during the progression from GERD to Barrett’s esophagus, and finally esophageal adenocarcinoma. To investigate how lactobacilli are able to colonize and survive in a bile-rich environment of the esophagus during GERD, we first exposed three Lactobacillus species (L. acidophilus, L. plantarum, and L. fermentum) to cholate/deoxycholate bile salts or ox-bile as a more physiological model for human reflux. All three species exhibited bile resistance, in addition to bile adaptation after pre-exposure to sub-lethal concentrations. When assessed for changes in bacterial cell surface hydrophobicity, an indicator for bacterial adhesion to various surfaces, both bile types led to an increase of hydrophobicity in L. plantarum and L. fermentum, while L. acidophilus remained high. This provides mechanistic insight into how Lactobacillus species' attachment and colonization remain during reflux-related diseases. Next, we assessed the host-microbe interactions between lactobacilli and esophageal cells and the role these probiotic organisms may have in disease prevention. Acidic bile salts can induce inflammation and DNA damage to esophageal tissue through ROS during GERD, yet we found that the presence of lactobacilli co-cultured with bile-treated esophageal epithelial cells aids in the repair of bile-induced DNA damage in addition to NFKB reductions. To further investigate the host-microbe interactions, we supplemented epithelial cells with lactobacilli postbiotic metabolites and assessed cell viability during 48 hours of growth. Our current preliminary data show that postbiotic supplementation increases cell viability, providing insight into why lactobacilli are present within the normal and diseased human esophagus. This study demonstrates how the colonization of the esophagus during GERD with lactobacilli is based on their adaptability and survival due to changes in hydrophobicity thereby sustaining attachment. Furthermore, the anti-genotoxic and anti-inflammatory effects these organisms exhibit make them of significant interest in the prevention of Barrett’s esophagus and esophageal adenocarcinoma in patients with GERD. Citation Format: Joshua Bernard, Divya Joshi, Claudia Andl. The anti-genotoxic function of Lactobacillus species in the context of bile-mediated DNA damage and inflammation in experimental models of GERD. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4233.