Various peripheral mechanisms have been implicated in the pathogenesis of irritable bowel syndrome, including intraluminal intestinal irritants, alteration in the bowel microbiome, enteroendocrine-cell products, and susceptibility to inflammation. Recent evidence is summarized in the latest review in our Mechanisms of Diseases series.
IBS affects 10 to 20% of the population. Specific peripheral mechanisms result in symptoms of IBS, including abnormal colonic transit and rectal evacuation; intraluminal intestinal irritants, such as maldigested carbohydrates (producing short-chain fatty acids) or fats, an excess of bile acids, and gluten intolerance; alterations in the microbiome; enteroendocrine-cell products; and genetic susceptibility to inflammation or altered bile acid synthesis.
• What are the typical symptoms that support a diagnosis of IBS?
The diagnosis of IBS is traditionally based on symptoms of recurrent abdominal pain or discomfort at least 3 days per month in the previous 3 months, in association with two or more of the following: improvement with defecation, an onset associated with a change in the frequency of bowel movements, or an onset associated with a change in the form (appearance) of stool.
• What other conditions should be considered in a patient who presents with a presumed diagnosis of IBS?
Fecal tests (e.g., measurements of fecal calprotectin and lactoferrin levels) or colonic visualization (e.g., colonoscopy) may be indicated clinically to rule out inflammatory bowel disease and neoplastic diseases. Patients who do not have a response to simple education and symptomatic remedies should undergo tests to identify causative factors, including tests of colonic transit and rectal evacuation in patients with constipation-predominant IBS and tests for carbohydrate or fat maldigestion (leading to the formation of short-chain fatty acids), increased bile acid synthesis or loss, and, possibly, dietary intolerance (e.g., gluten) in patients with diarrhea-predominant IBS.
Morning Report Questions
Q: What treatment options are available for patients with IBS?
A: About 25% of patients with constipation-predominant IBS (range among studies, 5 to 46) have slow colonic transit. Treatment with intestinal secretagogues (e.g., lubiprostone and linaclotide) or prokinetic agents (e.g., tegaserod) is effective in relieving constipation and associated IBS symptoms such as pain and bloating. Randomized, controlled trials of the nonabsorbed antibiotic rifaximin have shown a benefit in the treatment of IBS (without constipation) and a meta-analysis has demonstrated the efficacy of probiotics, particularly for abdominal pain and bloating. Dietary measures may also be helpful. The fat content of a meal, rather than the carbohydrate content, appears to have a key role in sensations of discomfort and pain.
Q: According to the authors, what are some of the physiological mechanisms involved in IBS?
A: The authors postulate a role of immune activation and altered bowel barrier function in a subgroup of patients with IBS, which has been associated with increased intestinal permeability. Factors associated with increased mucosal permeability and IBS include cow’s milk allergy, previous nonspecific infection, atopic disease (e.g., rhinoconjunctivitis, rhinitis, and eczema), stress, and dietary fat. A high-fat diet results in gut-derived endotoxemia and may contribute to the immune activation observed in some patients with IBS. The link between increased mucosal permeability and IBS is supported by the observation that increased permeability enhances mucosal inflammation and activates local reflex mechanisms, stimulating secretion and sensory pathways that lead to increased visceral sensation.