Irritable Bowel Syndrome

Educational Objectives

The goal of this program is to improve the management of irritable bowel syndrome (IBS). After hearing and assimi­lating this program, the clinician will be better able to:

1.   Discuss the 4 theories about the etiology of IBS.

2.   Recognize the importance of stress management, sleep, and exercise in the management of IBS.

3.   Explain the role of diet in IBS.

4.   Describe the association between celiac diseaseand IBS.

5.   Discuss the role of fiber and probiotics in the management of IBS.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of in­terest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgments

Dr. Lawson was recorded at the 2008 Update in Gastroenterology and Hepatology, held July 12-13, 2008, in Monterey, CA, and sponsored by the University of California, Davis, Health System, Office of Continuing Medical Education, and Di­vision of Gastroenterology and Hepatology, Department of Internal Medicine. Dr. McAbee was recorded at the Gastroen­terology and Hepatology Update 2008, held September 19, 2008, in Nashville, TN, and sponsored by the Vanderbilt University School of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, and Vanderbilt Division of Continuing Medical Education. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Overview of Irritable Bowel Syndrome (IBS)

Michael J. Lawson, MD, Clinical Professor of Medicine, University of California, Davis, School of Medicine

Definition: no structural or biochemical abnormality; tests usually negative; typically, recurrent abdominal pain with disturbed defecation (alternating diarrhea and constipation [more common]); bloating common feature, as is re­ferred pain; present in 15% to 20% of population; only one-third of patients seek medical care

Physiology: patients with IBS have pain at much lower volume with rectosigmoid balloon distention (visceral hypersensitiv­ity); “pain gate”  —  anterior cingulate gyrus in midbrain; protects brain from excessive “information”; controlled by prefron­tal cortex; problems with anterior cingulate gyrus seen in patients with IBS; unable to fire as actively when experiencing pain; more visceral hypersensitivity when IBS patient under stress; stress, sleep, and exercise  —  stress controlled through ed­ucation and cognitive behavioral therapy (CBT), with success rates of 85% to nearly 100%; sleep patterns important; pa­tients complain of fatigue and have increased rapid eye movement (REM) activity; comorbidities (eg, fibromyalgia, temporomandibular joint [TMJ] disorder, migraine) share same sleep disturbances; tricyclic antidepressants (TCAs)  —  low doses used; shut pain gate, reducing visceral hypersensitivity and improving sleep patterns; improve energy and allow pa­tient to exercise (key); pain gate has multiple endorphin receptors blocked by exercise; IBS patients who exercise vigorously do better than those who exercise moderately or not at all

Nonulcer dyspepsia (NUD): often misdiagnosed as gastroesophageal reflux disease; patients often present with pain after eating, bloating, and frequent belching, worsening with stress (“irritable” stomach) and may eventually de­velop IBS symptoms; stomach unable to accommodate (relax); bloating  —  due to compensation for inability to ac­commodate; diaphragm pushed down and abdominal muscles contorted; resolves under general anesthesia

Suspected etiologies: 4 theories; postinfectious  —  30% of cases originate with acute infection; in epidemics, those infected 5 times more likely to have IBS in following year and 7 times more likely to have NUD; speaker does not recommend treat­ment with antibiotics; bacterial overgrowth not seen in culture of small bowel; breath testing nonspecific and somewhat un­reliable; »30% of patients with IBS have positive breath test; prospective studies show poor results for treatment with antibiotics; genetics  —  serotonin reuptake transporter gene up- or downregulated due to polymorphisms in certain patients with IBS; 20% concordance rate in monozygotic twins; motility disturbance  —variable findings; patient with IBS generates more pressure in sigmoid colon; environment  —  abused children more likely to develop IBS; difficult to treat, more comor­bidities, and more likely to present at tertiary health care centers; majority of patients who present for treatment suffer from somatoform disorders; study of twins by Levy found concordance rate in monozygotic twins 79.2%; more significant if mother has IBS than if identical twin has IBS, suggesting that environment plays big role

Diagnosis: Manning criteria  —  abdominal pain with alternating diarrhea and constipation; pain relieved by bowel movement; feeling of incomplete evacuation; comorbidities important and drive patients into other specialties; patients “catastrophize” symptoms; physician should be confident in diagnosis (correct 96% of time); diagnostic tests  —  test for fecal leukocytes ac­ceptable, but unreliable in presence of Clostridium difficile; presence of fecal fat means malabsorption of fat due to pancre­atic insufficiency or more commonly, celiac sprue (masquerades as IBS); test for antibodies reliable; consider flexible sigmoidoscopy in any patient with blood in stool; should investigate individuals >50 yr of age with new-onset symptoms with sigmoidoscopy; education and reassurance  —  effective and therapeutic; study found that when physician explained condition at length, including link between symptoms and stress, patients less likely to return, less likely to have diarrhea, anxiety, and depression, and have less abdominal pain

Diet: gastrocolic reflex  —  controllable; amplified in IBS, and patient blames food; fiber  —  not answer for IBS; pa­tients should not take fiber if it makes them feel worse; choose more easily digestible fiber and introduce slowly

Constipation-predominant IBS (IBS-C): increasing oral liquids has little value; fiber supplements and lactulose ex­acerbate bloating; emulsified mineral oil (Kondremul)  — lubricating laxative; palatable; ideal for children with en­copresis; polyethylene glycol 3350 (Miralax)  —  best; effective; lubiprostone  —  stimulates chloride channel secretion; tablet taken bid

Management: psychologic treatments  —  ideal; stress management, sleep, and exercise; CBT  —  some studies show no change in stress levels in patients with IBS, but improvement of symptoms seen; affects pain gate without necessarily af­fecting stress levels; hypnosis and relaxation training used; self-guided imagery effective; drug therapy  —  low tolerance seen in patients with IBS; side effects often seen; all drugs have high placebo response in IBS (£80%, commonly 40%); high placebo response also seen with surgery, eg, cholecystectomy; enteric-coated peppermint oil  —  relaxes smooth mus­cle of gastrointestinal (GI) tract and lower esophageal sphincter; released slowly through colon; no better than placebo; perianal burning often seen; loperamide  —  does not cross blood-brain barrier; patients with severe diarrhea may take £8 tablets daily (no overdose seen); causes constipation

Serotonin: 95% found in GI tract (5% in central nervous system); stimulates peristalsis by proximal contractions and distal relaxation; controls sensitivity and secretion; target of therapy; abnormalities in serotonin metabolism often seen in IBS patients; alosetron  —  serotonin antagonist; ideal for diarrhea-predominant IBS (IBS-D); causes susceptibility to ischemic colitis, leading to death; withdrawn from market; 60% efficacy rate; tegaserod  —  serotonin agonist; effective for IBS-C; quick response in stool frequency; tachyphylaxis seen; withdrawn due to cardiac toxicity

IBS in children: patients often say symptoms started in childhood; 20% to 30% of school-age children have IBS symp­toms (called recurrent abdominal pain, but part of IBS spectrum); treatment program for adolescents  —  average age 12 yr; included parents; consisted of exercise, CBT, stability ball, education for mothers and children, and nutrition coun­seling; Rome scores greatly improved at 6 mo; significant decrease in pain scores and increase in quality of life; 85% reduction in visits for IBS in year after program

Dietary Factors in IBS

Stephanie A. McAbee, MD, Assistant Professor of Medicine, Division of Gastroenterology, Vanderbilt Univer­sity Medical Center, Nashville, TN

Etiology: food intolerance frequently perceived cause for symptoms; patients typically find pain worse in postprandial pe­riod

Food triggers: postprandial diarrhea often attributed to “overactive” gastrocolic reflex; caffeine gut stimulant and con­tributes to symptoms of IBS; dietary fat important modulator of gut function (may contribute to bloating); compared to controls, patients with IBS exhibit increased retention of gas infused into small bowel after administration of enteral fat; fat content increases visceral hypersensitivity in patients with IBS; study showed increased sensitivity to colonic balloon distention after duodenal lipid infusion in IBS patients

Food intolerance: passage of substances into colon causes inflow of fluid into colon, resulting in diarrhea or pain; malab­sorbed carbohydrates (eg, lactose, sorbitol, fructose) most commonly implicated; carbohydrate malabsorption  —  patients with IBS vs controls; 90% of all subjects had malabsorption of ³1 sugar; symptom scores higher in those with IBS, with 40% improving after elimination of sugar from diet; lactose intolerance  —  due to insufficient lactase in mucosa of small bowel; residual lactose fermented by colonic microflora; patients able to tolerate small amounts of lactose but become symp­tomatic with larger amounts; however, many patients with IBS who think they are lactose intolerant not true lactose malab­sorbers; several series show minimal benefit from lactose-free diet, even when intolerance  objectively identified in IBS patients; in study of 30 patients with self-reported lactose intolerance, 21 identified as malabsorbers by hydrogen breath test­ing; when blinded to 240 mL of regular milk or lactose-free milk daily, no difference in symptom scores found; many IBS patients already ingesting <240 mL of milk daily; one study in Netherlands found benefit in eliminating lactose; possible role for lactose malabsorption in 5% of children with chronic diarrhea due to viral gastroenteritis (not shown in adults with postinfectious IBS); fructose intolerance  —  in study of 80 patients with IBS, one-third had positive fructose breath test; »50% compliant with fructose-free diet; in compliant patients, pain, belching, bloating, and diarrhea improved (no improve­ment in noncompliant participants)

Food allergy: true hypersensitivity, with immunologic response to food product; difficult to diagnose; exclusion diet and reintroduction of food only way to evaluate role in IBS; IgE-mediated response; rare and occurs shortly after ingestion (most commonly nuts, shellfish, or fish); not well studied in IBS; most studies used IgE-mediated skin-prick or radioallergosorbent (RAST) testing; subsequent studies unable to link positive response to double-blind challenge in IBS patients with positive skin testing to certain foods; study data  —  of 80 IBS patients, only 11 had positive skin testing to foods for which they reported intolerances; injection of food antigens submucosally in colon produced wheal-and-flare reaction in IBS patients (not in controls); local mucosal response associated with mast cell activation but skin-prick testing and IgE negative; symptom improvement also reported on exclusion diet; sev­eral studies showed response to cromolyn (mast cell stabilizer); IgG and IgA antibodies found in patients with ce­liac disease; however, role of antibodies in other food allergies controversial; IgG antibodies to foods common in normal population and often considered physiologic; meta-analysis  — looked at elimination diet followed by food rechallenge; problem food found in 58% of cases (included milk, wheat, and eggs); however, celiac disease and lac­tose intolerance not excluded; positive responses to exclusion diets 15% to 71%; higher response rates seen in pa­tients with IBS-D

Increased gas production: dependent on delivery of fermentable carbohydrate to colon and colonic bacterial flora; study  —  6 patients; found total hydrogen secretion greater in IBS patients at baseline; hydrogen production and symptom scores decreased after 2-wk diet excluding poorly absorbed carbohydrates, eg, wheat, potatoes, onions, dairy; after lactulose, breath hydrogen greater on standard than on exclusion diet, suggesting alteration of colonic flora

Role of fiber: American Gastroenterological Association (AGA) guidelines recommend increased dietary fiber as first-line treatment for IBS-C; recommended daily intake 20 to 30 g daily; average diet in United States <10 g/day; proposed mechanisms of action include enhancement of water-holding properties in stool, formation of gels to pro­vide lubrication, stool bulking, and binding of bile; soluble fiber  —  derived from fruits and grains, eg, psyllium; considered “prebiotic” (nurtures colonic flora); fermented by bacteria in colon to form short-chain fatty acids used as fuel for colonocytes; stool bulking due to increase in fecal bacterial mass; insoluble fiber  —  mostly in grains, eg, wheat bran; partially fermented by colonic bacteria; major physiologic effect to hold water, thus bulking stool; syn­thetic fiber  —  polycarbophil and methylcellulose; hypothesized to cause less bloating (not metabolized by bacteria to same degree); in survey of 100 IBS patients treated with wheat bran, only 10% improved, and 55% reported worsening symptoms, particularly bloating; systematic review found no convincing evidence of improvement in global IBS symptom scores, compared to placebo; although role of fiber in treatment of constipation well estab­lished, value in other subsets of IBS less clear

IBS and celiac disease: high prevalence of wheat fiber intolerance in patients with IBS, therefore, benefit from glu­ten-free diet may also be due to fiber exclusion; data suggest role for microscopic inflammation in IBS; mucosal immune system activation in postinfectious IBS and IBS-D; correlation between pain and activated mast cells near colonic nerves; patients with inflammatory bowel disease (IBD) in remission have higher prevalence of IBS symp­toms; patients with celiac disease and underlying inflammation possibly at higher risk for IBS

Role of probiotics: live microbial organisms administered in foods or supplements; pass through GI tract unaffected by acid, bile, or proteolytic enzymes, enter small bowel or colon, and multiply on epithelial cell surfaces; effects on host beneficial; most derived from food sources, especially cultured milk products; initial studies of probiotic species sug­gested potential efficacy in GI diseases, including IBD (particularly pouchitis), antibiotic-related diarrhea, C difficile di­arrhea, infectious diarrhea, and hepatic encephalopathy; proposed beneficial effects  —  ferment soluble fiber in colon to produce short-chain fatty acids which provide nutrients to colonocytes and aid in cholesterol metabolism; some species of Lactobacillus and Bifidobacterium deconjugate and absorb bile acids; provide barrier to harmful organisms by adher­ence to intestinal epithelium; production of substances that have antibiotic effect; stimulate immune processes in host by induction of protective and suppression of proinflammatory cytokines; modulation of pain perception (some Lacto­bacillus strains induce expression of opioid and cannabinoid receptors in intestinal epithelial cells); differ in ability to resist gastric and bile acids, colonize GI tract, and stimulate cytokine production; benefits observed with one species or combination of species not generalizable to other species; yogurt commonly recommended source of probiotics; many of live cultures unable to survive in acidic environment; concentration of active cultures often low, and lack standardiza­tion among different preparations; modest benefit seen in studies with positive results; possible that benefit present in certain subgroups of IBS patients (IBS-D); study  —  Lactobacillus plantarum vs placebo; flatulence significantly re­duced in probiotic group; abdominal pain reduced to similar extent in both groups; at 12 mo, overall GI function score higher in treatment group; no difference in bloating; study  —  Lactobacillus casei GG vs placebo; no difference in pain, urgency, or bleeding, although trend seen towards reduction in number of loose stools in IBS-D group; study  —  VSL#3 (composite of 8 species) vs placebo; no significant difference in colonic transit time compared to baseline; bloating re­duced in probiotic group; no difference in pain, gas, or urgency; subsequent study showed slowed colonic transit time compared to placebo, with significant reduction in flatulence, but no difference in bloating, pain, or stool-related symp­toms

Suggested Reading

Atkinson W et al: Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut 53:1459, 2004; Dear KL et al: Do interventions which reduce colonic bacterial fermentation improve symptoms of ir­ritable bowel syndrome? Dig Dis Sci 50:758, 2005; Faure C et al: Visceral hypersensitivity in irritable bowel syndrome: does it really normalize over time? Gastroenterology 132:464, 2007; Ford AC et al: Efficacy of antidepressants and psy­chological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58:367, 2009; Ford AC et al: Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis. Arch Intern Med 169:651, 2009; Gershon MD et al: The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132:397, 2007; Guilarte M et al: Diar­rhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 56:203, 2007; Isolauri E et al: Food allergy in irritable bowel syndrome: new facts and old fallacies. Gut 53:1391, 2004; Kurland JE et al: Prevalence of irritable bowel syndrome and depression in fibromyalgia. Dig Dis Sci 51:454, 2006; Lin HC: Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA 292:852, 2004; Spiller R: Probiotics: an ideal anti-inflammatory treatment for IBS? Gastroenterology 128:783, 2005; Talley NJ: Genes and environment in irritable bowel syndrome: one step forward. Gut 55:1694, 2006.