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

Abstract

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. Lactobacillus species are commensal organisms known for their probiotic and antioxidant characteristics in the healthy esophagus. This prompted us to investigate how Lactobacilli 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 Lactobacillus species (L. acidophilus, L. plantarum, and L. fermentum) 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 Lactobacilli 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 Lactobacilli, making them of significant interest in the prevention of Barrett’s esophagus and esophageal adenocarcinoma in patients with GERD.

Trypsin activates PAR2 inhibits the expression of tight junction protein through activation of NLRP3 inflammasome pathway in gastroesophageal reflux disease

“…ROS can cause DNA damage in GERD and produce 8-oxo-G, which promotes NF-kB pathway and pro-inflammatory genes, meanwhile chronic inflammation perpetuates DNA damage [29] . Occludin interacts with death-inducing signaling complex (DISC) to initiate cell death.…”

Exploring the Microbiome in Gastric Cancer: Assessing Potential Implications and Contextualizing Microorganisms beyond H. pylori and Epstein-Barr Virus

“…Upon oxidative DNA damage in gastric cancer cells, activation of the DNA damage response pathway occurred. Particularly, Chk1 and Chk2 phosphorylation signified the activation of Chk1 and Chk2, which could stop the cell cycle, potentially leading to mitotic exit and genomic instability [19] Aided in the restoration of DNA damage caused by reactive oxygen species generated by bile [20] Came across reactive oxygen species generated by the host's innate immune response against persisters, culminating to DNA damage [21] Immune Evasion and Immune System Evaded pattern recognition receptor detection by evading recognition by toll-like receptors (TLRs) and inhibiting signaling mediated by c-type lectin (DC-SIGN) [22] Enhanced immune system through strengthening the cytotoxic impact of natural killer (NK) cells and impacted the production of various essential pro-inflammatory cytokines, such as IL-1β, IL-4, IL-5, IL-6, IL-8, and IL-13 [23] The breakdown of inflammatory hyaluronan fragments produced by the host into disaccharides enabled Group B Streptococcus to avoid being detected by the immune system [24] Table 1. Cont.…”