<i>Lactobacillus</i> sp. Facilitate the Repair of DNA Damage Caused by Bile-Induced Reactive Oxygen Species in Experimental Models of Gastroesophageal Reflux Disease

oleh: Joshua N. Bernard, Vikram Chinnaiyan, Jasmine Almeda, Alma Catala-Valentin, Claudia D. Andl

Format: Article
Diterbitkan: MDPI AG 2023-06-01

Deskripsi

Gastroesophageal reflux disease (GERD) leads to the accumulation of bile-induced reactive oxygen species and oxidative stress in esophageal tissues, causing inflammation and DNA damage. The progression sequence from healthy esophagus to GERD and eventually cancer is associated with a microbiome shift. <i>Lactobacillus</i> species are commensal organisms known for their probiotic and antioxidant characteristics in the healthy esophagus. This prompted us to investigate how <i>Lactobacilli</i> survive in a bile-rich environment during GERD, and to identify their interaction with the bile-injured esophageal cells. To model human reflux conditions, we exposed three <i>Lactobacillus</i> species (<i>L. acidophilus</i>, <i>L. plantarum</i>, and <i>L. fermentum</i>) to bile. All species were tolerant to bile possibly enabling them to colonize the esophageal epithelium under GERD conditions. Next, we assessed the antioxidant potential of <i>Lactobacilli</i> and role in bile injury repair: we measured bile-induced DNA damage using the ROS marker 8-oxo guanine and COMET assay. Lactobacillus addition after bile injury accelerated repair of bile-induced DNA damage through recruitment of pH2AX/RAD51 and reduced NFκB-associated inflammation in esophageal cells. This study demonstrated anti-genotoxic and anti-inflammatory effects of <i>Lactobacilli</i>, making them of significant interest in the prevention of Barrett’s esophagus and esophageal adenocarcinoma in patients with GERD.