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General introduction 17 1 symptoms and are usually suggested next if further treatment is necessary. 77 General dietary and lifestyle modifications include less intake of e.g. alcohol, caffeine, spicy-, fat-, lactose containing or other foods that trigger symptoms, as well as decreasing meal portions and/or number of meals a day, modifying dietary fiber intake, and increasing physical activity. 20,76 In patients with bloating and or flatulence as predominant symptoms that respond inadequately to general dietary modifications, a diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) may be beneficial. 78 This diet ultimately aims at a balanced intake of FODMAP containing foods that do not, or solely to an acceptable extent, trigger symptoms, in combination with low intake or avoidance of FODMAP containing foods that trigger severe symptoms. If dietary and lifestyle modifications provide inadequate results, psychological and/or pharmacological treatment should be considered. As psychosocial factors can influence GI symptoms and vice versa, various psychological treatments can be tried, such as cognitive behavioral therapy, gut-directed hypnotherapy, mindfulness-based therapy and psychodynamic therapy. When combined with medical and dietary therapies, gut-directed-psychotherapies collectively have a favorable number needed to treat of 4 and are at low risk for adverse events. 79 Nevertheless, the clinical implementation is still limited due to a lack of trained therapists in some geographical areas. 80 If pharmacological treatment is preferred and diarrhea is the main predominant symptom, treatment options include the antidiarrheal drug loperamide 76 , the antibiotic rifaximin 81 and bile-acid binders. 82 In addition, recent pharmacological advancements have led to the development of eluxadoline, a mixed agonist of μ-opioid and ĸ-opioid receptors and an antagonist of ð-opioid receptors, for the treatment of diarrhea and to a lesser extent abdominal pain in IBS-D patients. 83 Eluxadoline treatment should, however, be closely monitored due to serious side effects ( e.g. pancreatitis and sphincter of Oddi spasms). 84 Pharmacological treatment of constipation often begins with the osmotic laxative polyethylene glycol. 76 Second-line options that have become available recently as a result of pharmacological developments include linaclotide 85 , and plecanatide 86 , and tenapanor. 87 Linaclotide and plecanatide are guanylate-cyclase-C agonists that increase fluid secretion into the intestinal lumen to hydrate stools and possibly also reduce abdominal pain. Tenapanor is a minimally absorbed, small molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3 that increases fluid and sodium into the intestinal lumen. 88 IBS patients that suffer from mixed type IBS should preferably