Irritable bowel syndrome is the commonest health problem in hospital outpatient clinics and in private health care facilities and represents a big challenge for patients and physicians. This presentation discusses a different aspect of the disease from pathophysiology, clinical presentation and management

1. Irritable bowel
syndrome
Monkez M Yousif MD AGAF
BY

3. Earliest descriptions of symptoms defining IBS
• 1849 – W Cumming
“The bowels are at
one time constipated,
at another lax, in the
same person.
How the disease has
two such different symptoms I
do not profess to explain. . . .”
⚫ 1962 – Chaudhary & Truelove
• Irritable colon syndrome
⚫ 1966 – CJ DeLor
• Irritable bowel syndrome
IBS – History
⚫ Other historical terms
– mucous colitis
– colonic spasm
– neurogenic mucous colitis
– irritable colon
– unstable colon
– nervous colon
– spastic colon
– nervous colitis
– spastic colitis
⚫ 1978 – Manning Criteria
Irritable colon syndrome
⚫ 1992, 1999, 2006,2016 – Rome I,II,III,IV Criteria
Irritable bowel syndrome

4. Manning’s Criteria 1978
Three or more features should have been present for
at least 6 months:
➢ Pain relieved by defecation.
➢ Pain onset associated with more frequent stools.
➢ Looser stools with pain onset.
➢ Abdominal distension.
➢ Mucus in the stool.
➢ A feeling of incomplete evacuation after defecation.

5. Rome IV diagnostic criteria for irritable bowel
syndrome 2016
• Recurrent abdominal pain on average at least 1 d/wk in the
last 3 mo, associated with 2 or more of the following criteria
1. Related to defecation
2. Associated with a change in the frequency of stool
3. Associated with a change in the form (appearance) of stool
• These criteria should be fulfilled for the last 3 months with
symptom onset at least 6 months before diagnosis.
Gastroenterology 2016;150:1393–407.

6. Subtypes of IBS
• IBS-D (IBS with diarrhea): where ≥ 25% of bowel movements include diarrhea
• IBS-C (IBS with constipation): presence of hard or lumpy stools with ≥ 25% of
bowel movements
• IBS-M (mixed IBS): patients with alternating diarrhea (≥ 25% of bowel movements)
and constipation (≥ 25% of bowel movements)
• Unsub-typed IBS: insufficient abnormality of stool consistency to meet the
definitions for IBS-C, -D or -M

7. Epidemiology
• IBS is the most commonly diagnosed GI condition , accounting for ~30% of
all referrals to gastroenterologists
• Approximately 10-20% of adults & adolescents have symptoms consistent
with IBS
• IBS accounts for the second highest cause of work absenteeism after the
common cold
• First symptoms are typically seen before 45 years of age.
• The ratio of women: men with IBS is ~2:1

8. IBS prevalence in population studies around the world
Clin. Gastroenterol. Hepatol. 10, 712–721.e4 (2012).

9. Association between
IBS and other disorders

10. Risk factors for IBS

11. Pathophysiology
• Despite extensive investigation, the pathophysiology of IBS is not
clearly understood but factors that contribute to IBS indifferent subsets
of patients include:
̶ A history of psychosocial factors (anxiety, depression, phobias and daily
stressful events)
̶ Altered GI motility
̶ Increased visceral hypersensitivity to distention
̶ Altered gut microflora (infection may affect gut permeability & the enteric
nervous system)
̶ Increased gut permeability
̶ Increased levels of pro-inflammatory cytokines
̶ Dysregulation of the interaction between the gut and central nervous system.

14. The Brain-Gut-Microbiota Axis
• The Brain-Gut-Microbiota Axis plays an important role in
regulating the behavior of the GI tract. The major components of
the axis include the:
A. Central Nervous System (CNS)
1. HPA Axis
2. Cortical areas
3. Brainstem
B. Autonomic nervous system
• Efferent & afferent nerve fibers to smooth muscle & glands
C. Enteric Nervous System
• functions autonomously in the absence of external input, but is modulated by the
CNS
• utilizes over 30 neurotransmitters including acetylcholine, dopamine & serotonin
• communicates with the CNS through parasympathetic & sympathetic nerves
D. Gut Wall
• layers of smooth muscle, glands, epithelium
E. Intestinal Microbiome

16. Brain-Gut-Microbiota Axis

17. • Under normal physiological conditions, signals from
the GI tract influence the brain, and the brain in turn
modulates various aspects of GI physiology including
changes in GI motility & secretion.
• This axis is an important bidirectional communication
system for regulating food intake, digestion, gut
sensations, and bowel movements.
• Structural or functional disruptions of this axis can
result in multiple types of GI disorders, including IBS

18. • Imaging experiments utilizing MRI and PET have
shown that patients with IBS exhibit a visceral
hypersensitivity, resulting in enhanced cerebral
cortical responses to balloon distension of the
descending colon compared to patients without IBS .
Central responses to visceral signals are responsible
for the perception of pain.

19. • Serotonin (5-HT) is an important molecule used by multiple
neural systems in both the brain and gut.
• Several different 5-HT receptors have been identified to play
different roles in the GI physiology, and the pathophysiology
of IBS. In particular, 5-HT3 receptors are found on enteric
afferent nerves , and when stimulated by 5-HT released by
enterochromaffin cells in response to distension of the GI
wall, produce cortical responses resulting in nausea,
vomiting and abdominal pain.

20. Alarm features for IBS

21. A diagnostic algorithm for patients with IBS

22. Treatment
•IBS Treatment is "Symptomatic"

24. MILD TO MODERATE SYMPTOMS
• Education, Stress Management, Diet & Exercice
• Education regarding the proposed mechanisms of IBS helps patients understand
the rationale for chronic treatment. Although evidence is lacking, cognitive-
behavioral therapy may help change maladaptive thinking patterns that could
underlie somatic symptoms.
• Bloating-related pain may be relieved by a diet low in fermentable oligo-, di-,
and mono-saccharides and polyols (FODMAPs), an exclusion of gas-producing
foods. Such foods are poorly absorbed and are osmotically active in the
intestinal lumen when they are fermented, resulting in abdominal bloating and
pain.
• Physical activity (20 to 60 minutes of moderate to vigorous activity 3-5 days per
week) may produce clinical improvement in the severity of IBS compared to
control groups

26. Antidiarrheals or Laxatives
• First-line drug therapy for IBS depends on the symptoms, and includes:
• IBS-D: opioid antidiarrheal agent (loperamide)
• loperamide is a non-prescription opioid agonist that does not cross the blood-brain barrier and has no
analgesic properties or potential for addiction.
• in the gut it inhibits the release of acetylcholine and prostaglandins, thereby reducing peristalsis and slowing
intestinal transit time, which also favorably affects water and electrolyte movement through the bowel.
• IBS-D: bile acid sequestrant antidiarrheal agent
• there is weak evidence supporting the use of bile acid sequestrants (cholestyramine, colestipol, colesevelam)
as antidiarrheals in IBS-D.
• Up to 50% of patients with IBS-D have bile acid malabsorption, and bile acids cause diarrhea by stimulating
colonic activity and secretion.
• In one small clinical trial (24 patients with IBS-D), colesevelam slowed GI transit time by four hours
compared to placebo.
• IBS-C: laxatives (osmotic laxatives)
• osmotic laxatives such as polyethylene glycol (PEG) (Movicol) are inexpensive & widely available osmotic
laxatives exert their effect by increasing osmotic pressure within the GI tract, causing more water to enter
the lumen. This results in bowel distention, increased peristalsis, and evacuation.

27. • Patients treated with PEG have significantly more spontaneous bowel
movements, improvement in stool consistency, and reduction in the
severity of straining.
• Osmotic laxatives, however, do not reduce the severity of bloating or
abdominal pain compared to placebo in IBS.
• Treatment with other laxatives such as soluble fiber supplements is
more controversial, since clinical trials have failed to demonstrate a
clear benefit

28. PERSISTENT or SEVERE SYMPTOMS
• Alosetron (Lotronex 0.5 & 1 mg tablets) For Severe Refractory IBS-D
• Serotonin (5-HT) plays an important role in both the regulation of
GI motility and the activation of visceral pain 5-HT3 receptors.
• As a result, inhibition of 5-HT3 receptors by alosetron is a rational
approach to reduce the unpleasant visceral sensations associated
with IBS. Blockade of central 5-HT3 receptors by alosetron also
reduces the CNS response to visceral afferent stimulation. In
addition, the blockade of 5-HT3 receptors on cholinergic nerve
endings inhibits colonic motility
• “Interestingly” alosetron is FDA-approved for use in women only.
While there is some evidence that it may also be effective in men,
data are limited

30. Rifaximin for IBS-D
• The ecology of fecal microflora is complex. There is limited evidence
that changes in microflora may underly IBS-D, at least in some
patients.
• A meta-analysis of five randomized trials determined that rifaximin (a
minimally absorbed antibiotic) was more efficacious than placebo in
reducing bloating and abdominal pain in patients with IBS-D.
• Rifaximin is a broad-spectrum antibiotic (related to rifampin) that acts
primarily in the GI tract when taken orally, due to its very low
bioavailability (poor absorption).

31. Drugs That Stimulate Chloride Secretion for IBS-C
• There are two prescription drugs that are FDA-approved for the treatment of
persistent IBS-related constipation:
• Lubiprostone (Lubicont 8 & 24 mcg capsules)
• Prostaglandin activator of the intestinal type 2 Cl channel
• stimulates secretion of chloride-rich fluid into the intestine, which increases intestinal motility & shortens
intestinal transit time.
• Dose: 8 mcg twice daily for IBS and 24 mcg twice daily for idiopathic chronic constipation.
• Linaclotide (Linzess, Constella Capsules)
• indirectly stimulates chloride secretion by stimulating guanylyl cyclase C in the intestinal epithelium
• binds to & activates guanylyl cyclase C on the luminal intestinal epithelium, resulting in increased cGMP
• increased cGMP actives CFTR (the cystic fibrosis transmembrane conductance regulator)
• activation of CFTR results in a chloride-rich secretion and acceleration of intestinal transit causes an
increase of 1-2 bowel movements per week

32. PAIN & DISCOMFORT
• Antispasmodics
• Chronic abdominal pain that frequently occurs in both
IBS-C & IBS-D may respond to:
• Antimuscarinic antispasmodics (dicyclomine, hyoscyamine) which antagonize the
effect of vagal stimulation to enhance intestinal motility.
• Peppermint oil which exerts an inhibitory effect on calcium channels of intestinal
smooth muscle), thereby reducing motility.
• Pinaverium bromide: It is a calcium antagonist which inhibits the influx of calcium
into intestinal smooth muscle cells.

33. • Tricyclic Antidepressants
• Tricyclic antidepressants (TCAs)(e.g. amitriptyline, imipramine, nortriptyline) may
provide benefit in patients with IBS-D.
• The doses of TCAs used are lower than those that affect mood but are sufficient to alter
central processing of visceral (pain-related) afferent information. The anticholinergic
effects of TCAs and other antimuscarinic agents may also help reduce stool frequency &
liquidity, which may be of benefit in IBS-D.
• TCAs should be used cautiously (if at all) in patients with IBS-C due to their inhibitory effect on
GI motility.
• SSRIs
• SSRIs may also be useful in IBS, but there is less evidence supporting their efficacy
• The 2015 British Clinical guidelines for IBS recommended SSRI use only if TCAs are ineffective
• SSRIs “may” be of more utility in patients with comorbid depression, or with IBS-C (SSRIs
more frequently cause diarrhea vs constipation). In contrast, TCAs may be better tolerated in
IBS-D due to their anticholinergic effect to reduce gut motility.

34. Mechanisms of action of
different drugs used for
the treatment of IBS.

35. ACG Clinical Guideline: Management of
Irritable Bowel Syndrome
Am J Gastroenterol 2021;116:17–44.
https://doi.org/10.14309/ajg.0000000000001036

36. 1. We recommend that serologic testing be performed
to rule out celiac disease in patients with IBS and
diarrhea symptoms.
Strong recommendation; moderate quality of evidence.
- IgA anti-tissue transglutaminase or
- endomysial antibody.

37. 2. We suggest that fecal calprotectin (or fecal
lactoferrin) and CRP be checked in patients without
alarm features and with suspected IBS and diarrhea
symptoms to rule out inflammatory bowel disease.
Strong recommendation; moderate quality of evidence.

38. 3. We recommend against routine stool testing for
enteric pathogens in all patients with IBS.
Conditional recommendation; low quality of evidence.

39. Risk factors for Giardiasis
̶ Children in childcare settings.
̶ Close contacts of people with Giardiasis (for example, people living in the
same household) or people who care for those sick with Giardiasis
̶ People who drink water or use ice made from places where Giardia may live
(for example, untreated or improperly treated water from lakes, streams, or
wells)
̶ Backpackers, hikers, and campers who drink unsafe water or who do not
practice good hygiene (for example, proper handwashing)
̶ People who swallow water while swimming and playing in recreational water
̶ People exposed to human feces through sexual contact
̶ International travelers where Giardia may live, especially in lakes, rivers,
springs, ponds, and streams

40. 4. We recommend against routine colonoscopy in
patients with IBS symptoms younger than 45 years
without warning signs.
Conditional recommendation; low quality of evidence.

41. 5. We suggest a positive diagnostic strategy as
compared to a diagnostic strategy of exclusion for
patients with symptoms of IBSs to improve time to
initiate appropriate therapy.
Consensus recommendation
Although a validated definition does not exist, a positive diagnostic
strategy involves a careful history, physical examination, and the use of a
standard definition to make a diagnosis, with limited diagnostic tests.

42. 6. We recommend a positive diagnostic strategy as
compared to a diagnostic strategy of exclusion for
patients with symptoms of IBSs to improve cost-
effectiveness.
Strong recommendation; high quality of evidence.

43. 7. We suggest that categorizing patients based on an
accurate IBS subtype improves patient therapy.
Consensus recommendation

44. To accurately categorize a patient with IBS by subtype, we recommend the following:
1. Predominant stool consistency can be determined based on the Bristol Stool
Form Scale (BSFS).
2. Determine patient’s primary stool consistency only on the days s/he reports
abnormal bowel movements. This determination should be made when patient
is off of therapy(ies) that could affect bowel pattern. Daily diaries should be
performed for 2 weeks for the most accurate assessment.
3. Once the pattern of stool consistency is determined, subtype decisions can be
made according to the Rome IV criteria (4):
a) IBS-C: 25% of bowel movements associated with BSFS 1 or 2 with BSFS 6 or 7
occurring less than 25%.
b) IBS-D: 25% of bowel movements associated with BSFS 6 or 7 with less than
25% of bowel movements with BSFS 1 or 2.
c) IBS-M: 25% of bowel movements associated with BSFS 1 or 2 and.25% of
bowel movements associated with BSFS 6 or 7.
d) IBS-U: cannot be determined.

45. Bristol stool chart
The Bristol Stool Chart or Bristol Stool Scale is
a medical aid designed to classify stools into
seven groups.
▪ Type 1-2 indicate constipation,
▪ Type 3-4 are ideal stools as they are easier
to pass, and
▪ Type 5-7 may indicate diarrhoea and
urgency.

46. ̶ Most therapeutic agents used to treat IBS symptoms were
developed with an emphasis on 1 specific IBS subtype;
therefore, although not studied prospectively, assigning
the wrong subtype to a patient could result in a treatment
approach that worsens symptoms.
̶ Currently, there are no approved medications for the
treatment of IBS-M or IBS-U; this is an important gap to be
addressed in future research.

47. 8. We do not recommend testing for food allergies and
food sensitivities in all patients with IBS unless there
are reproducible symptoms concerning for a food
allergy.
Consensus recommendation
➢ The low prevalence of food allergies in adults, the finding that patients with IBS are not more likely
to develop food allergies, and poor diagnostic test characteristics (e.g., serum IgE levels and the
skin prick test), make it neither efficient nor cost-effective to test patients with IBS for food
allergies.

48. 9. We suggest that ano-rectal physiology testing be
performed in patients with IBS and symptoms
suggestive of a pelvic floor disorder and/or
refractory constipation not responsive to standard
medical therapy.
Consensus recommendation
Given the high estimated prevalence of pelvic floor disorders in all IBS subtypes, we propose first using
standard therapies for IBS targeting both abdominal pain and the predominant bowel habit.
In patients with abnormal rectal examinations concerning for dyssynergia or those refractory to
conventional treatments and with pelvic floor symptoms, we suggest anorectal physiology testing with
ARM and BET and/or defecography to identify patients who could be treated with biofeedback therapy.

49. Dyssynergic Defecation
Clinical symptoms, rectal examination
findings, and anorectal physiologic
testing suggestive of a pelvic floor
disorder

50. 10. We recommend a limited trial of a low FODMAP diet
in patients with IBS to improve global IBS symptoms.
Consensus recommendation

51. 11. We suggest that soluble, but not insoluble, fiber be
used to treat global IBS symptoms.
Strong recommendation; moderate quality of evidence.

52. • A widely accepted definition describes dietary fiber as all carbohydrates
that are neither digested nor absorbed in the small intestine.
• Dietary fiber has diverse effects in the GI tract involving the gut
microbiome, metabolism, transit time, stool consistency, and bile acid
absorption.
• Dietary fiber is frequently recommended to improve symptoms in patients
with IBS, particularly when constipation is the predominant complaint.
• Soluble fiber is found in psyllium (Metamucil, Sorbix), oat bran, barley,
and beans.
• Insoluble fiber is found in wheat bran, whole grains, and some vegetables.
• Fibers that exert laxative effects tend to increase stool water content and
resist colonic fermentation. Conversely, fibers that ferment in the colon will
lose their water-holding capacity and produce gas that could aggravate
symptoms of bloating and flatulence.

53. 12. We recommend against the use of antispasmodics
for the treatment of global IBS symptoms.
Conditional recommendation; low quality of evidence.

54. 13. We suggest the use of peppermint to provide relief
of global IBS symptoms.
Conditional recommendation; low quality of evidence.

55. • Although the clinical benefits of peppermint oil for patients
with IBS have most often been attributed to blockade of
calcium channels and attendant smooth muscle relaxation,
several other potential explanations are mentioned
including:
̶ modulation of transient receptor potential voltage
channels with effects on visceral sensation,
̶ direct antimicrobial and anti-inflammatory effects, and
̶ modulation of psychosocial distress.

56. 14. We suggest against probiotics for the treatment of
global IBS symptoms.
Conditional recommendation; very low quality of evidence.

57. • The use of probiotics in the treatment of IBS is an important area of
research, given the importance of the intestinal microbiome in this
condition.
• However, interpreting the existing literature is problematic because of
small studies, the multiple types and strains of probiotics, the
inconsistent benefits on individual symptoms, and the lack of rigorous
trials based on US FDA endpoints.
• These challenges make meta-analysis difficult to perform and hard to
interpret. Future trials incorporating yet unidentified gut microbiome
biomarkers or metabolomic markers may improve probiotic efficacy.

58. 15. We suggest against PEG products to relieve global
IBS symptoms in those with IBS-C.
Conditional recommendation; low quality of evidence.

59. 16. We recommend the use of chloride channel
activators to treat global IBS-C symptoms.
Strong recommendations; moderate quality of evidence.
Amitiza (Lubiprostone)

60. 17. We recommend the use of guanylate cyclase
activators to treat global IBS-C symptoms.
Strong recommendation; high quality of evidence.
Trulance (Plecanatide)
Linzess (Linaclotide)

61. 18. We suggest that the 5-HT4 agonist tegaserod be
used to treat IBS-C symptoms in women younger
than 65 years with #1 cardiovascular risk factors who
have not adequately responded to secretagogues.
Strong/conditional recommendation; low quality of evidence
Zelnorm (tegaserod)
Resolor (Prucalopride)

62. 19. We do not suggest the use of bile acid sequestrants
to treat global IBS-D symptoms.
Conditional recommendation; very low quality of evidence.

63. 20. We recommend the use of rifaximin to treat global
IBS-D symptoms.
Strong recommendation; moderate quality of evidence.

64. 21. We recommend that alosetron be used to relieve
global IBS-D symptoms in women with severe
symptoms who have failed conventional therapy.
Conditional recommendation; low quality of evidence.
Lotronex, (alosetron)

65. 22. We suggest that mixed opioid agonists/antagonists
be used to treat global IBS-D symptoms.
Conditionalrecommendation; moderate quality of evidence.
Vibrezi(Eluxadoline)

66. 23. We recommend that tricyclic antidepressants be
used to treat global symptoms of IBS.
Strong recommendation; moderate quality of evidence.

68. 24. We suggest that gut-directed psychotherapies be
used to treat global IBS symptoms.
Conditional recommendations; very low quality of evidence.

69. 25. Using currently available evidence, we recommend
against the use of fecal transplant for the treatment
of global IBS symptoms.
Strong recommendation; very low quality of evidence.

70. Questions to be answered about IBS
• There are still significant gaps in our knowledge.
Future research is needed to
• better understand the role of the gut microbiome in patients with
IBS and to
• understand the genesis of visceral pain and to
• Identify biomarkers to predict treatment response.

71. 71
Monkez M Yousif

80. The roles of 5-HT3R
in diseases