Human Gastrogenic Lactobacillus Plantarum Lpf-01: A Promising Candidate for Nsaids-Induced Acute Erosive Hemorrhagic Gastritis

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used in clinical practice for a variety of applications. Many patients require long-term use of these medications. However, NSAIDs can also cause numerous adverse reactions, with gastrointestinal erosion, ulceration, and bleeding being the most common. Traditional treatments for gastric mucosal damage caused by NSAIDs primarily involve the use of proton pump inhibitors (PPIs) to reduce gastric acid secretion. However, long-term use of PPIs can also be associated with several side effects, including osteoporosis and fractures, vitamin B12 deficiency, and renal impairment. Additionally, research has found that long-term use of NSAIDs can lead to an imbalance in the gastric microbiota, and most probiotics cannot stably exist and function within the stomach. Therefore, this study introduces the concept of “treating gastric diseases through gastric microbiota,” aiming to explore the potential of Lactobacillus plantarum LPF-01, a human gastric-derived strain, in treating NSAIDs-induced acute erosive hemorrhagic gastritis. Methods: We treated a NSAIDs-induced (IND) acute erosive hemorrhagic gastritis model with LPF-01, ATCC, and PPI, followed by macroscopic and microscopic observations. A series of kits, immunohistochemistry, immunofluorescence, and Western blot experiments were conducted to detect gastric mucosal injury-related indicators before and after treatment. Additionally, flow cytometry was used to measure CD18 levels, and ELISA was employed to assess the expression of thrombosis and vasoconstriction factors. Results: Compared with the NSAID model group, LPF-01 and PPI groups showed a significant reduction in gastric mucosal injury and bleeding points, while the ATCC 8014 treatment group still exhibited considerable injury. Compared with the NSAID model group, the expression of mucins (MUC5AC and MUC6) in the LPF-01 and PPI groups was increased, while ATCC was ineffective. At the same time, LPF-01 has excellent antioxidant effects and can effectively protect the gastric mucosal barrier. Compared with the NSAID model group, the levels of gastric mucosal inflammatory factors in the LPF-01 and PPI groups were significantly reduced, and the expression of protective prostaglandin E2 (PGE2) and cyclooxygenase-1 (COX-1) in the LPF-01 group was significantly increased. Additionally, LPF-01 improved the reduction of barrier proteins (ZO-1 and Occludin) caused by IND, maintaining the integrity of the gastric mucosal barrier. Furthermore, compared with the NSAID model group, the LPF-01 group showed a significant reduction in the expression of adhesion molecules CD18 expressed by neutrophils, and the levels of endothelin-1 (ET-1), angiotensin II (Ang II), and leukotrienes in the blood, inhibiting the gastric mucosal thrombosis and vasoconstriction caused by NSAIDs, and enhancing the defensive and reparative functions of the gastric mucosal barrier. Conclusion: Human gastrogenic Lactobacillus LPF-01 can enhance the defensive and reparative functions of the gastric mucosal barrier and treat NSAIDs-induced acute erosive hemorrhagic gastritis by inhibiting the formation of gastric mucosal thrombosis and vasoconstriction caused by NSAIDs.