bismuth subsalicylate + dimethyl fumarate

**Bismuth subsalicylate + dimethyl fumarate** is a combination of two small-molecule drugs: bismuth subsalicylate, a gastroprotective, antimicrobial, and anti-inflammatory agent primarily used for gastrointestinal symptom relief, and dimethyl fumarate, an oral immunomodulatory small molecule approved for the treatment of relapsing multiple sclerosis. This combination has been investigated for reducing gastrointestinal side effects commonly associated with oral dimethyl fumarate (such as diarrhea and flatulence). Bismuth subsalicylate acts locally by hydrolyzing to bismuth and salicylic acid: bismuth remains minimally absorbed in the gut, where it exhibits antimicrobial activity (notably against Helicobacter pylori), impedes bacterial adhesion, decreases intestinal secretions, and reduces inflammation. Salicylic acid inhibits cyclooxygenase and prostaglandin formation, providing additional anti-inflammatory effects[2][4]. Dimethyl fumarate modulates immune cell responses via activation of the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway, reducing oxidative stress and inflammation. Clinical study PREVENT showed that while the combination does not significantly reduce the overall occurrence of gastrointestinal events in healthy subjects receiving dimethyl fumarate, it does lower the severity and incidence of flatulence and diarrhea, improving tolerability[1][3][5].