NSAIDs like ibuprofen work by blocking the action of enzymes — cyclooxygenase (COX)-1 and -2 to be specific — that are responsible for producing the fatty acids called prostaglandins in your system. In addition to triggering inflammation and fever, prostaglandins also help protect your gut lining by aiding the release of gut-protective mucus, according to functional medicine physician Dr. Amy Myers. According to a 2015 study published in eLife, prostaglandins also promote blood clotting, and when these functions of this fatty acid are inhibited, you are leaving your gut exposed to increased permeability, ulcers, bleeding, and perforation in the intestinal tract. 

“When there’s not enough mucus in your digestive tract, the acid erodes the surface of your stomach or small intestine, causing an ulcer. This open sore can bleed,” explained Dr. Myers. A compromised gut lining also means a leaky gut.

A leaky gut (harm-causing bacteria leaking into your bloodstream) brought on by long-term (and short-term) ibuprofen use can lead to a myriad of other medical concerns like allergies, autoimmune diseases, compromised immune system, depression, obesity, type 2 diabetes, heart disease, and cancer. Something else also happens with regular NSAID use and this has to do with your gut microbiome composition.