IBS AND PROBIOTICS
| DIAGNOSTIC AND THERAPEUTIC CONSIDERATIONS FOR IBS—Robert S. Fisher, MD, Professor, Department of
Medicine and Chief, Section of Gastroenterology and Digestive Disease Center, Temple University School of Medicine,
Philadelphia, PA
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| Definition of irritable bowel syndrome (IBS): abdominal pain or discomfort, usually centered around or below umbilicus;
chronic; characteristics—patient must have ≥2; symptoms relieved by defecation; change in frequency of defecation;
change in consistency of stools; endoscopy, x-ray, and biochemical studies normal; subtypes—IBS with
constipation; IBS with diarrhea; IBS with alternating diarrhea and constipation
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| Causes of IBS: motility disorders; altered gastrocolic reflex; altered gastroileal reflex; abnormal myoelectric activity in
rectosigmoid; visceral hypersensitivity—demonstrated by inflating balloon in rectosigmoid of patients with IBS
(pain and discomfort result from lower volumes than in normal patients); differences in brain metabolism demonstrated
on magnetic resonance imaging (MRI) and positron emission tomography (PET); depression or anxiety; infection; neurotransmitters
(eg, serotonin) affect secretion, motility, and visceral sensitivity
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| Differential diagnosis: cancer; mechanical obstruction; inflammatory bowel disease; diverticulitis; ischemic bowel disease;
red flags—history of anorexia or weight loss; positive family history of Crohn’s disease, ulcerative colitis, colon
cancer, or celiac sprue; higher likelihood of structural disorder in patients ≥50 yr of age; follow up on patients with physical
findings (eg, hepatosplenomegaly) or abnormal findings (eg, anemia); tissue transglutaminase antibody testing for patients
with diarrhea to rule out celiac sprue; diagnostic testing for patients with alarm symptoms—colonoscopy;
computed tomography (CT); small bowel x-ray; if negative, consider diagnosis of IBS
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| Management of symptoms: target predominant symptom; abdominal pain—antispasmodics (eg, anticholinergic
agents); tricyclic compounds; no specific antinociceptives for gastrointestinal (GI) tract; nonsteroidal anti-inflammatory
drugs (NSAIDs) can cause GI symptoms; opioids (“it’s a slippery slope once you start using them”); bloating and
distention—modify diet (eg, decrease lactose, eliminate sorbitol); antispasmodics; simethicone; activated charcoal; digestive
enzymes; antibiotics; diarrhea—dietary fiber; loperamide; diphenoxylate combined with atropine; cholestyramine;
constipation—dietary fiber; osmotic laxatives (eg, magnesia [Milk of Magnesia], lactulose, sorbitol, polyethylene glycol
[MiraLax], glycerin); stimulant laxatives (eg, cascara, senna, bisacodyl)
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| Therapy: counseling patients with IBS about diet, exercise, and stress management resulted in slight improvement (“not
very striking”); elimination diets followed by reintroduction of food groups to identify tolerable foods may be reasonable;
dietary fiber can soften stools but results in more bloating or flatulence; anticholinergics—1) 40 mg of dicyclomine
(Bentyl) qid resulted in change in abdominal pain and side effects; 2) few studies on hyoscyamine (Levsin/SL, Levbid,
Levsinex, IBS-Stat) show efficacy in treating IBS, but side-effect profile reasonable; tricyclic compounds—little data
available; low doses for patients with pain; suggested helpful by selected studies of small numbers of patients; first-generation
agents have higher incidence of side effects (eg, blurred vision, dry mouth, constipation) than second-generation
agents; selective serotonin reuptake inhibitors (SSRIs)—no data; may be useful in patients with depression and
IBS with constipation (side effects include diarrhea); psychologic interventions—cognitive behavioral therapy; psychodynamic
interpersonal psychotherapy; hypnotherapy; relaxation training; effective in some patients; alosetron
(Lotronex)—5-hydroxytryptamine-3 (5-HT3 ) antagonist; shown to decrease diarrhea and peristaltic reflex in small
bowel and colon; withdrawn returned to market due to side effects, but returned to market for highly selective use in IBS;
tegaserod (Zelnorm)—5-hydroxytryptamine-4 (5-HT4 ) agonist; studies showed improvement in well-being; stimulates
peristaltic reflex; side effects include diarrhea and headache
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| IBS IN CHILDREN AND ADOLESCENTS —John F. Pohl, MD, Associate Professor of Pediatrics, Texas A&M University
System Health Science Center, and Physician, Department of Pediatrics, Scott & White Hospital, Temple, TX
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| Presentation of IBS: can appear differently in children; all functional abdominal pain in children not IBS; refer to pediatric
gastroenterologist when child symptomatic for ≤12 mo with multiple diagnostic testing; negative tests reinforce
anxiety (positive outlook helpful)
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| Pathophysiology: bowel motility—altered with stress; may increase or decrease colon contraction; loss of migratory
motor complexes in intestine (often due to fasting); increased contraction after high-fat meal; visceral
hypersensitivity—pain receptors in area may be primed by infection or lumen contents; inherent differences in pain
modulation; psychosocial factors—patients with IBS have higher rate of psychiatric disease; childhood history of
abuse increases severity of symptoms; infection and inflammation—inflammatory mediators (eg, tumor necrosis
factor [TNF]-α) increase intestinal motility; increases risk of developing IBS; increased risk for IBS in patients with exposure
to infectious enteritis or inflammatory bowel disease
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| Red flags: patient history—pain away from umbilicus; pain associated with bowel habit changes; pain with nighttime
awakening; repetitive emesis (especially if bloody or bilious); constitutional symptoms (eg, fever, weight loss)
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 | Location of pain: right upper quadrant—consider gallstones or liver disease; epigastric—ulcer; pancreatitis; left
upper quadrant—usually not GI cause; consider urologic causes (eg, ureteropelvic junction [UPJ] obstruction);
right lower quadrant—appendicitis; infectious enteritis; development of Crohn’s disease; periumbilical pain—
recurrent abdominal pain (RAP); left lower quadrant—constipation; limited left-sided colitis; suprapubic—
urinary tract infection (UTI)
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| Physical examination: decrease in height velocity; organomegaly or abdominal mass; perirectal changes; joint swelling
or tenderness; unusual rash; pale mucosa or conjunctiva
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| Testing: laboratory—erythrocyte sedimentation rate; liver panel; amylase; lipase; β-human chorionic gonadotropin in
teenaged girls; antiendomysial antibody or tissue transglutaminase antibody testing; radiographic—abdominal flat plate
(kidneys, ureter, and bladder [KUB]); abdominal ultrasonography or CT; barium study; refer to gastroenterologist for endoscopy
with biopsy
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| Recurrent abdominal pain: 3 episodes of pain that interfere with activity in period ≥3 mo; affects 10% to 15% of
children, with slight predominance in girls; no organic cause; pain usually in periumbilical area; self-limited; rarely related
to meals; rarely awakens child from sleep; organicity of pain inversely proportional to number of school absences;
may develop into IBS; criteria for IBS—abdominal pain, often relieved with defecation; increased defecation at onset
of pain; changes in stool form at time of pain; passage of mucus; bloating with abdominal distention; no pathologic cause
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| Treatment modalities: placebo treatment can improve IBS symptoms in 20% to 50% of patients; psychotherapy—
helpful adjunct; useful for recognizing triggers of IBS; relaxation therapy; hypnotherapy; affects pain and diarrhea, but
not constipation; fiber supplementation—number of grams needed by child daily determined by age in years + 5
(maximum 20-25 g/day); osmotic laxatives—helpful; best to use when fiber ineffective or causes bloating; safe for
long-term use; mineral oil helpful but associated with malabsorption of fat-soluble vitamins and aspiration pneumonia
(do not use in children <7 yr of age or children with neurologic problems); lactulose; MiraLax (scheduled dosing or prn);
average long-term effective dose 0.7 g/kg per day); problem with underdosing or not using long enough; stimulant
laxatives—side effects (eg, cramping, dependence, tachyphylaxis); permanent disruption of enteric nervous system
with long-term use seen in animal models; “try to stick with the osmotic laxatives”
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| Treatment of IBS with diarrhea: opiate analogues effective; loperamide controls diarrhea but not pain; cholestyramine
useful for refractory diarrhea but can cause malabsorption of fat-soluble vitamins; antispasmodics—useful for increased
contractility after eating; taken 30 min before meal or every 4 hr prn; side effects include dry mouth, constipation, blurred vision,
fatigue, and urinary difficulty; contraindicated in patients with narrow-angle glaucoma; can decrease anxiety aspects of
IBS when combined with low-dose sedatives or benzodiazepines; hyoscyamine; dicyclomine; tricyclic
antidepressants—effective at low doses with no antidepressant effects; side effects include fatigue, somnolence, dry
mouth, and urinary retention; cardiac arrhythmias can occur with high doses; start low (eg, 10-20 mg of amitriptyline [“I
rarely go past 30 mg”]); SSRIs—treat depression well; minimal effect on pain threshold; useful for IBS with underlying
mood disorder; serotonin-3 receptors—increase motility, secretion, and sensation; antagonists useful for diarrhea-type
IBS; alosetron associated with high rate of ischemic colitis (strict guidelines for use); serotonin-4 receptors—increase
peristalsis and gastric emptying; agonists effective for constipation-type IBS; tegaserod effective for constipation-type IBS
for ≤12 wk; 2- and 6-mg tablets; adult dose 6 mg bid (start low); effective; expensive
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| Other agents: neomycin; herbal mixtures; peppermint oil may increase risk for gastroesophageal reflux disease (GERD);
leuprolide for menstrual-related IBS; itopride—used in Japan; dopamine D2 -receptor antagonist; anticholinergic effects;
studies found significant improvement in pain compared to placebo; probiotics—limited data about use in children
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| PREBIOTICS, PROBIOTICS, AND SYNBIOTICS —Lucinda A. Harris, Senior Associate Consultant, Division of Gastroenterology
and Hepatology, Mayo Clinic, Scottsdale, AZ
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| Definitions: prebiotics—nondigestible fermentable foods that promote healthy colonic flora; found in chicory, leeks,
wheat, and breast milk; probiotics—exogenous live bacteria; usually Lactobacillus and Bifidobacterium; introduced
into gut for healthful benefit; synbiotics—combination of prebiotics and probiotics; eg, Activia yogurt; stimulates
indigenous bacteria and increases survival of probiotic
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| Normal enteric flora: >400 bacterial species in gut; aerobic to anaerobic transition along intestine—in duodenum,
≈1000 bacteria (usually Streptococcus); number increases and type changes until primarily facultative anaerobic bacteria
found in colon
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| How probiotics appear to work: change mucus production and increase barrier to “bad” bacteria in gut; inhibit growth
of pathogenic bacteria; block attachment of pathogenic bacteria to intestine; prevent invasion of pathogenic bacteria into epithelium
by changing biofilm or acting at tight junctions; alter immune response by increasing secretory IgA or stimulating
regulatory T-cell responses
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| Available probiotics: Belgian study found 70% of probiotics on market not viable bacteria; use probiotics that underwent
trials and/or have standardization of viability
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| Atopic dermatitis: probiotics theorized to decrease incidence by increasing Bifidobacterium and decreasing
Clostridia; 1) Lactobacillus rhamnosus strain GG given to pregnant mothers before delivery and to infants during
first 6 mo after birth; incidence of atopic dermatitis in probiotics group 50% of that in placebo group; 2) longer study in
larger group of patients showed good duration of effect; studies in older children saw long duration of effect of probiotic
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| Cholesterol: results of studies in humans conflicting and controversial, but ≈5% increase in high-density lipoprotein
(HDL) and decrease in low-density lipoprotein (LDL) and triglycerides shown; proposed mechanisms—cholesterol
assimilated into bacterial cell rather than entering bloodstream; deconjugation of cholesterol by bile salts and bacteria; increased
cholesterol uptake by LDL receptor pathway in liver
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| Anticancer effects of probiotics: little direct evidence; evidence suggests probiotics might inhibit transformation of
procarcinogens, decrease number of mutagenic compounds, produce antimutagenic compounds, suppress growth of procarcinogenic
bacteria, and enhance immune function; inverse relationship between consumption of fermented dairy products
and incidence of colon and breast cancer observed in epidemiologic studies; bladder cancer—patients given Lactobacillus
casei within 2 wk of diagnosis of superficial bladder cancer; 1-yr recurrence of tumor in probiotic group 50%, in
placebo group 83%
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| Nonalcoholic steatohepatitis: mice with overexpression of TNF-α given VSL#3 (probiotic consisting of Streptococcus
, Lactobacillus, and Bifidobacterium); inflammation, steatohepatitis, and liver damage decreased; mechanism
hypothesized independent of TNF
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| Helicobacter pylori: probiotics may decrease density of H pylori in stomach; evidence probiotics, in addition to 3-drug
regimen (includes 2 antibiotics), decrease side effects; adjunctive and prophylactic role possible
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| GI infections: eg, rotavirus; studies using L casei and L rhamnosus showed no effect; decreased incidence of rotavirus
infection seen in longer (15 mo) studies in breast-fed infants; prophylactic role possible; more studies needed
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| Irritable bowel syndrome: small number of patients with IBS may respond to probiotics; 1) study saw decrease in
bloating with use of probiotics; 2) Lactobacillus acidophilus shown to affect pain, bloating, and number of bowel
movements; 3) Lactobacillus salivarius compared to Bifidobacterium infantis; Bifidobacterium decreased pain,
bloating, and global symptoms of IBS; normalization of ratio of serum levels of interleukin (IL)-10 and IL-12 suggests
modulation of inflammatory response of gut to probiotics
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| Other conditions: acute pancreatitis—patients given Lactobacillus plantarium had lower rates of severe infections
and abscesses; radiation-induced diarrhea—L rhamnosus decreased stool frequency and improved stool consistency;
small intestinal bacterial overgrowth—L plantarium in children with short bowel syndrome prevented
recurrence of symptoms following antibiotic treatment; small study showed use of 2 strains reduced diarrhea in patients on
medication (but may have relapsed when medication discontinued); studies with Saccharomyces boulardii (Florastor)
and Lactobacillus showed no benefit; pouchitis—VSL#3 shown to help maintain antibiotic-induced remission; results
in Crohn’s disease and ulcerative colitis more controversial; no role for inducing remission
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Educational Objectives
| The goal of this program is to educate the listener about irritable bowel syndrome (IBS) and the use of probiotics. After
hearing and assimilating this program, the participant will be better able to:
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| 1. Select therapeutic agents to target predominant symptoms of IBS.
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| 2. Counsel parents and patients about effects of diet and stress on IBS.
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| 3. Identify red flags in patients who present with abdominal pain.
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| 4. Describe proposed mechanisms of action of prebiotics, probiotics, and synbiotics.
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| 5. Discuss the possible role of probiotics in conditions such as atopic dermatitis, cancer, and IBS.
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Discussed on This Program
Alosetron HCl [Lotronex]
Amitriptyline HCl [Elavil]
Bisacodyl (several trade names)
Cascara sagrada (Rhamnus purshiana) [Aromatic Cascara Fluidextract; Cascara Aromatic]
Charcoal, activated [Actidose-Aqua, Actidose with Sorbitol, CharcoAid, CharcoAid 2000, Liqui-Char]
Cholestyramine [Cholestyramine Light, Prevalite, Questran, Questran Light]
Dicyclomine HCl [Antispas, Bentyl, Byclomine, Dibent, Dilomine, Di-Spaz, Or-Tyl]
Diphenoxylate HCl with atropine sulfate [Logen, Lomanate, Lomotil, Lonox]
Glycerin (glycerol) [Fleet Babylax, Colace, Ophthalgan, Osmoglyn, Sani-Supp]
Guar gum [Benefiber]
Hyoscyamine sulfate (L-hyoscyamine sulfate) (several trade names)
Itopride HCl (not available in United States)
Lactobacillus [Bacid, Kala, Lactinex, MoreDophilus, Pro-Bionate, Superdophilus]
Lactulose [Cephulac, Cholac, Chronulac, Constilac, Constulose, Duphalac, Enulose]
Leuprolide acetate (several trade names)
Loperamide HCl (several trade names)
Magnesia (magnesium hydroxide) [several trade names]
Mineral oil [Kondremul Plain, Milkinol]
Neomycin sulfate [Mycifradin, Neo-fradin, Neo-Tabs]
Polycarbophil [Bulk Forming Fiber Laxative, Equalactin, FiberCon, Fiber-Lax, FiberNorm, Konsyl Fiber, Mitrolan]
Polyethylene glycol solution [MiraLax]
Psyllium (several trade names)
Senna (Cassia acutifolia or Cassia angustifolia)
Sennosides (several trade names)
Simethicone (several trade names)
Sorbitol
Tegaserod maleate [Zelnorm]
Suggested Reading
Badia X et al: Burden of illness in irritable bowel syndrome comparing Rome I and Rome II criteria. Pharmacoeconomics
20:749, 2002; Creed F: How do SSRIs help patients with irritable bowel syndrome? Gut 55:1065, 2006;
Dunne C et al: Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human
clinical trials. Antonie Van Leeuwenhoek 76:279, 1999; Gueimonde M et al: Effect of maternal consumption
of lactobacillus GG on transfer and establishment of fecal bifidobacterial microbiota in neonates. J Pediatr Gastroenterol
Nutr 42:166, 2006; Jones R et al: A positive diagnosis in irritable bowel syndrome. Int J Clin Pract 60:870,
2006; Kalliomaki M et al: Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled
trial. Lancet 361:1869, 2003; Kim HJ et al: A randomized controlled trial of a probiotic combination VSL# 3
and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil 17:687, 2005; Leung WK et al:
Treatment of diarrhea-predominant irritable bowel syndrome with traditional chinese herbal medicine: a randomized placebo-controlled
trial. Am J Gastroenterol 101:1574, 2006; Mearin F et al: Irritable bowel syndrome subtypes according
to bowel habit: revisiting the alternating subtype. Eur J Gastroenterol Hepatol 15:165, 2003; O'Mahony L et
al: Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.
Gastroenterology 128:541, 2005; Ringel Y: New directions in brain imaging research in functional gastrointestinal
disorders. Dig Dis24:278, 2006; Tack J et al: Systematic review: the efficacy of treatments for irritable bowel
syndrome - a European perspective. Aliment Pharmacol Ther 24:183, 2006; Vanderhoof JA et al: Current and potential
uses of probiotics. Ann Allergy Asthma Immunol 93:S33, 2004; Vanderhoof JA et al: Pediatric applications
of probiotics. Gastroenterol Clin North Am 34:451, 2005; Whitehead WE et al: Tolerance for rectosigmoid distention
in irritable bowel syndrome. Gastroenterology 98:1187, 1990; Wildi SM et al: Chronic abdominal pain: not
always irritable bowel syndrome. Dig Dis Sci 51:1049, 2006; Youssef NN et al: Pediatric Gastrointestinal Motility -
Future Directions and Challenges. Dig Dis 24:308, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Fisher is on the Speakers’ Bureau for Novartis Pharmaceuticals Corp., Janssen Pharmaceutical, Eisai Inc., and
Santarus, Inc. Dr. Harris has received research support from Novartis Pharmaceuticals Corp.
Dr. Fisher was recorded in Lancaster, PA, at the 29th Annual Fall Family Practice Review, presented September 25-
30, 2005, by Temple University School of Medicine and Lancaster General Hospital. Dr. Pohl spoke in San Antonio, TX, at
Adolescent Health Conference, presented April 27-29, 2006, by the Children’s Hospital at Scott & White and Texas
A&M University System, Health Science Center, College of Medicine. Dr. Harris was recorded in Phoenix, AZ, on April
29, 2006, at Clinical Reviews 2006: A Primary Care and Internal Medicine Update, presented by Mayo Clinic
College of Medicine at Scottsdale, AZ. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
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