Gut homeostasis, injury, and healing: New therapeutic targets

Figure 2 Non-steroidal anti-inflammatory drugs induce mucosal injury in the upper and lower gastrointestinal tract by two distinct mechanisms. In addition to principal luminal aggressors such as acid, pepsin, Helicobacter pylori in the stomach and acid, bile, and pathogens in the small intestine, nonsteroidal anti-inflammatory drugs (NSAIDs) increase mucosal damage in both upper and lower GI by two different mechanisms. In the stomach, the inhibition of COX-1 by NSAIDs reduces prostaglandin secretion which in turn reduces mucus and bicarbonate secretion and increases acid secretion, resulting in increased permeability and eventually mucosal damage. In the small intestine, NSAIDs bind to bile in the enterohepatic circulation. This potentiates the mucosal damage caused by bile. NSAIDs also increase mucosal damage in the small intestine by altering the gut microbiota. The NSAID-associated increase in enteric gram-negative bacteria appears to contribute to intestinal lesions by increasing inflammation. NSAIDs: Nonsteroidal anti-inflammatory drugs.