Therapeutic strategy for IBS and FD based on pathophysiology

Classically, irritable bowel syndrome (IBS) is diagnosed by asking a few key questions (Rome criteria), ruling out the presence of alarm features and applying judicious testing (e.g. celiac serology). However, advances in understanding the pathophysiology suggest a blood test for IBS may be in reach and within 10 years may be routine. Functional dyspepsia (FD) remains a diagnosis of exclusion but the identification of duodenal eosinophilia in a subset with early satiety and abdominal pain has opened up potential new avenues for diagnosis and treatment. Medical options are currently based on predominant symptoms, and treatment is symptom based rather than pathophysiologically driven, but this is arguably beginning to change. Pathophysiologically based treatments that work locally in the gut rather than systemically include linaclotide, a guanylate cyclase-C activator for IBS with constipation. Inflammation marks a subset with IBS, including mast cell infiltration in the small and large intestine. This is associated with increased gut permeability and mucosal immune activation with cytokine elevation that may drive the extra-intestinal manifestations of IBS (e.g. anxiety, fatigue). Steroids and 5-ASA have proven disappointing in randomized controlled trials. Mast cell stabilizers are not of proven benefit but antihistamine data look more promising. Increased risk of IBS occurs after gastroenteritis, and pre-existing anxiety and depression are a major risk factor for post infectious IBS. It has been hypothesized the site of infection and inflammation determines the outcome (IBS or FD or overlap). Excess small bowel bacteria have been documented in IBS by quantitative culture studies. Abnormal colonic flora also occurs in IBS. Only one drug is known to temporarily alter the natural history of IBS (rifaximin, with a 10% therapeutic gain). Select probiotics may be beneficial. New data indicate we should consider diet intervention early (low FODMAP, or possibly a gluten free diet in non-celiac patients), and prescribe regular exercise in IBS. Diet reduces bacterial substrate, reducing gas production and pain and bloating. Exercise may reduce inflammation. In FD, antisecretory therapy improves pain in a minority but the mechanism is unknown. Proton pump inhibitors inhibit eotaxin and cytokines possibly modulating duodenal eosinophilia. Acotiamide improves post-prandial distress symptoms. Buspirone relaxes the gastric fundus and appears beneficial. In patients failing first line therapies, antidepressants are superior to placebo in IBS; tricyclics but not SSRIs are probably efficacious in FD through central mechanisms.