1. Management of IBS : State of the art
Randhir Sud
Chairman
Institute of Digestive & Hepato-biliary Sciences
Medanta the Medicity
Gurgaon (Delhi NCR)

2. Case Capsule TC 32 yrs male H/O abdominal discomfort
Urge to pass stools after eating meals > 2 yrs
Stools are pasty but have no blood
There is mucus in stools & feeling of incomplete evacuation
What further questions you need to ask him ?

3. Case capsule Nocturnal symptoms Anorexia Weight loss Fever
Family h/o colitis or colon cancer
Is there relief in discomfort with passage of stools NO No
Yes

4. Case Capsule Physical exam : essentially normal P/R : Normal
Investigations :
CBC : Hb – 13.5gm/dl TLC 4700 ESR 24
Total Proteins / Alb 6.5gms/ 3.8gms
T3 T4 TSH -- Normal
Ferritin and serum iron normal
Sr B-12 levels low
Vit D3 levels very low

5. Case Capsule What is the diagnosis ? IBS D/D Colitis ? IBD
Diverticulosis coli
Colonic malignancy
SRUS
IBS type D
No blood , lack of nocturnal symps
No fever ? Diarrhea
No bld , No wt loss symps >2yrs
H/o digital evacuation

6. Special Investigations
Sigmoidoscopy/ colono scopy
Barium studies
M/R /CT enterography
Rectal manometery
If family h/o Ca colon, weight loss , bleeding PR , onset after 50 yrs
Not of value. ?Enema for Diverticulosis
If pain is severe and/or fever or bleed
Urgency and difficult stool passage

7. Tips for physicians Look for
Lactose intolerance
Celiac disease
Thyroid state
Drugs like laxative abuse , Metformin, Ca channel blockers
Fecal Calprotectin can differentiate from organic bowel disease

8. Irritable Bowel Syndrome
Chronic or recurrent GI symptoms
Lower abdominal pain/discomfort
Altered bowel habits
Bloating
Not explained by structural or biochemical abnormalities

9. IBS Clinical Subgroups
Constipation predominant
Diarrhea predominant
Alternating constipation/diarrhea
IBS – C
IBS – D
IBS – M

10. Rome II Criteria for IBS
At least 12 weeks or more, which need not be
consecutive, in the preceding 12 months, of
abdominal discomfort or pain that has 2 out
of 3 features:
Relieved by defecation
Onset associated with a change in frequency of stool
Onset associated with a change in consistency (appearance) of stool
Gut

11. Rome IV criteria for IBS
Recurrent abdominal pain on average at least 1 day a week in the last 3 months associated with two or more of the following:
1.Related to defecation
2. Associated with a change in a frequency of stool
3. Associated with a change in form of stool.
Symptoms must have started at least 6 months ago

12. Epidemiology of IBS in US (15% to 20% of Population)
CONFIDENTIAL
Epidemiology of IBS in US (15% to 20% of Population)
Specialists 5%
Primary care
15%
Nonconsulters
80%
25% to 50% of referrals to GIs are IBS

13. IBS in India vs west

14. IBS Symptoms Reduce Patient Well Being
Abdominal
pain
Reduced sense of
well being
Altered bowel
habits
Cramps
Bloating
Constipation
Diarrhea
Urgency
Abstinence from work
Doctors visits
Investigations & cost

15. Evolution of mechanistic hypotheses in IBS
5-HT mediated visceral
sensitivity and gut motility
Brain-gut interaction
Visceral hypersensitivity
The physiological understanding of IBS has evolved over the years. At one stage, IBS was described as a syndrome characterized by visceral hypersensitivity and abnormal gut motility.1 Studies using rectosigmoid balloon distension have shown that IBS patients have a significantly lower threshold for visceral pain than do healthy controls.2,3
The CNS regulates intestinal motor and sensory activity, and it was hypothesized that perhaps the interaction between the brain and gut altered the perception of pain in patients with IBS. A central concept to this theory is the development of hyperexcitability of neurons in the dorsal horn.4 This hyperexcitability can develop either in response to peripheral tissue irritation or to influences originating from the brain stem. It was then postulated that IBS may be a result of a disruption in the coordination of these centers.1
Knowing that 5-HT receptors may inhibit the activation of pain pathways in the peripheral nervous system led researchers to examine the role of 5-HT in IBS.5
References:
1. Drossman DA. Review article: an integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(suppl 2):3-14.
2. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut. 1973;14:
3. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci. June 1980;25:
4. Mayer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology. July 1994;107:
5. Prior A, Read W. Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5-HT3-receptor antagonist, in patients with irritable bowel syndrome. Aliment Pharmacol Ther ;7:
Abnormal motility
1950
2000
References: 1. Drossman. Aliment Pharmacol Ther. 1999;13(suppl 2): Prior and Read. Aliment Pharmacol Ther. 1993;7:

16. Pathophysiology of IBS: A bio-psychosocial disorder
Biological
Altered GI motor activity
Altered visceral sensation
Psychosocial
Behavioral
Cognitive
Emotional

17. IBS: patho-physiology
Visceral hypersensitivity
Increased visceral afferent response to normal as well as noxious stimuli
Mediators include
5-HT, bradykinin, tachykinins, CGRP, and neurotropins
Primary motility disorder of GI tract
Mediated by 5-HT, acetylcholine, ATP, motilin, nitric oxide, somatostatin, substance P, and VIP
Recent data suggest that there may be several mediators involved in visceral sensitivity and motility, one of which is 5-HT.1,2
References:
1. Bueno L, Fiormonti J, Delvaux M, Frexinos J. Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology. May 1997;112:
2. Goyal RK, Hirano I. Review article: the enteric nervous sytem. N Engl J Med. April 1996;334:
References: 1. Bueno et al. Gastroenterology. May 1997;112: Goyal and Hirano. N Engl J Med. April 1996;334:

18. Physiological distribution of 5-HT
CNS – 5%
5-HT has been implicated both as a neurotransmitter and as a paracrine signaling molecule in the bowel.1 It serves as a neurotransmitter in bowel nociceptive afferent (sensory) fibers, and this has been a major focus of recent research.2
5-hydroxytryptamine is distributed throughout the gut, predominantly within enterochromaffin cells in the mucosal crypts and, to a lesser extent, within the nerve fibers of the myenteric and submucosal plexuses. The concentration of 5-HT in the bowel is substantially greater than that in the brain.1
Although there are many neurotransmitters in the CNS and the gut, 5-HT has received some considerable attention. It is well established that about 95% of the body’s 5-HT is synthesized and stored in the enterochromaffin cells of the gut.1
References:
1. Gershon MD. Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.
2. Everhart JE, Renault PF. Irritable bowel syndrome in office-based practice in the United States. Gastroenterology. April 1991;100:
GI tract – 95%
– enterochromaffin cells
– neuronal
Reference: Gershon. Aliment Pharmacol Ther. 1999;13(suppl 2):15-30.

19. Comparison of pain thresholds of IBS patients and controls
Pain produced by rectosigmoid balloon distension 60
IBS 40
% Reporting Pain 20
Studies have demonstrated that patients with IBS have a heightened state of visceral sensitivity.1 In 1980, Whitehead et al evaluated pain thresholds of a total of 25 IBS patients and 20 healthy controls. By distending a rectosigmoid balloon in a stepwise fashion, the investigators found that pain thresholds in IBS patients were significantly lower than in controls (P<0.05).2 Studies evaluating the pain thresholds of other GI disorders involving the esophagus3 and stomach4 have shown similar findings.
References:
1. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut. 1973;14:
2. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci. 1980;25:6:
3. Richter JE, Barish CF, Castell DO. Abnormal sensory perception in patients with esophageal chest pain. Gastroenterology. October 1986;91:
4. Mearin F, Cucala M, Azpiroz F, Malagelada J-R. The origin of symptoms on the brain- gut axis in fuctional dyspepsia. Gastroenterology. October 1991;101:
Normal 20 60
100
140
180
Rectosigmoid balloon volume (mL)
Reference: From Whitehead et al. Dig Dis Sci. June 1980;25: With permission.

20. New knowledge in IBS Post infectious IBS
Micro-inflammation as trigger for hypersensitivity
Small intestinal bacterial overgrowth SIBO
Dysbiosis ( altered microbiota ) in colon

21. Altered gastrointestinal microbiome
Small intestinal bacterial overgrowth (SIBO) is quantitative alteration of the gut microbiota that may results in symptoms of IBS
The role of SIBO in IBS has been supported by evidence :
SIBO on breath testing is prevalent in pts of IBS
Treatment of presumed SIBO results in improvements in global symptoms of IBS, abdominal pain, bloating, and diarrhea

22. Make a positive diagnosis
Identify abdominal pain as dominant symptom with altered bowel function
Look for “red flags”
Perform diagnostic tests/physical exam to rule out organic disease
Make/confirm diagnosis
Precision in diagnosing IBS has been enhanced and simplified through the use of symptom-based criteria.
If a patient presents with chronic (12 weeks) bowel function disorders including abdominal pain as the dominant symptom with altered bowel function, a diagnosis of IBS is quite likely. To rule out an alternative or coexisting diagnosis, look for red flags such as weight loss, rectal bleeding, or anemia. Next, order laboratory studies and perform a physical exam to confirm the absence of organic disease.1
Once the diagnosis has been confirmed, initiate a treatment program and follow up in 3 to 6 weeks.2
References:
1. Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. Can Med Assoc J. July 1999;161:
2. American Gastroenterological Association. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology. June 1997;112:
Initiate treatment program as part of diagnostic approach
Follow up in 3 to 6 weeks
References: 1. Paterson et al. Can Med Assoc J. July 1999;161: American Gastroenterological Association. Gastroenterology. June 1997;112:

23. Treatment Approach
The 2009 American College of Gastroenterologists (ACG) evidence-based position statement on the management of IBS does not recommend laboratory testing or diagnostic imaging in patients younger than 50 years with typical IBS symptoms and without “alarm features”.

24. “Red flags” may suggest an alternative or coexisting diagnosis
Additional diagnostic screening needed for atypical presentations such as
Anemia
Fever
Persistent diarrhea
Rectal bleeding
Severe constipation
Weight loss
Nocturnal symptoms of pain and abnormal bowel function
Family history of GI cancer, inflammatory bowel disease, or celiac disease
New onset of symptoms in patients 50+ years of age
To rule out alternative or coexisting disease, there are some red flags that may appear either during the intake or physical exam that would suggest a condition other than IBS.
Reference:
Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. Can Med Assoc J. July 1999;161:
Reference: Paterson et al. Can Med Assoc J. July 1999;161:

25. IBS is a chronic disorder with no specific organic cause
IBS is a chronic disorder with no specific organic cause. The patient's confidence in the physician's diagnosis, explanation, and reassurance are vital therapeutic tools.
Dietary Modification
Psychosocial Treatment
Medications

26. Dietary implications in IBS
Mechanisms for food intolerance
Osmotically active – sorbitol
Carbohydrate intolerance = lactose / fructose
GI tract stimulants – caffeine
Food allergies
Enhanced gastro-colic reflex
Colonic fermentation

27. Diet in IBS
FODMAPS : Fermentable Oligosaccharides , Disaccharides, Monosaccharides and Polyols
Fiber in diet

28. Low and high FODMAP diets

29. Low and high FODMAP diets

30. Fiber in diet for IBS Insoluble fiber :Whole grains , wheat bran
Soluble : oats , psyllium and flax seed
Moayyedi P et al Am J Gast 2014
Meta-analysis of 14 studies 906 pts:
Significant benefit of soluble fiber but not of insoluble fiber in global symptoms of IBS

31. Exercise in IBS
Exercise improves QOL in many medical conditions : fibromyalgia , depression Ca colon
Exercise improves gas transit and defaecatory function
RCT -102 pts; Johannasson E . Am J Gast 2011
Exercise minutes 3 to 5 times / week
Significant improvement in exercise group

32. Suggested sequence of pharmacological treatment for IBS

33. Recommendations based on guidelines

34. Probiotics in IBS 6 systematic reviews : modest benefit
Global symps and Pain , bloating stool consistency and frequency
No benefit in flatulance and diarrhea
Problems:
Which probiotic for which symptom
How much and how long

35. Probiotics in IBS
Lactobacillus shown to help in diarrhea pre-dominant IBS
Bifidocaterium infantilis : systematic review shows definite benefit in abdominal pain, bloating and stool pattern
Benefits are bacteria specific and proper studies are needed to ascertain specific use

36. IBS-D R/o lactose intolerance: breath test or elimination
R/o Celiac disease , thyrotoxicosis, Metformin
2 weeks of Rifaximin 550mgs tid
Romasetron 5mgs od for upto 12 weeks
Loperamide as per need
Anti-cholenergics do help in pain and decrease motility
Tricyclics
BEL extract

37. IBS-C Soluble fiber PEG Picosulfate Lubiprostone 8mgs twice
Linaclotide ( not yet available )
SSRI,s if associated depression
For pain use mebaverine and not anti-cholinergics

38. New Drugs
Rifaximin
Approved in May 2015 by the U.S. (FDA) for treatment of IBS with diarrhea (IBS-D) in adults.
SIBO & post infectious IBS are rationale
It works by reducing or altering bacteria in the gut.
Improvement in diarrhea with 2 week course

39. IBS - D
Eluxadoline
It is a new drug which activates receptors in the nervous system that can lessen bowel contractions.
It is prescribed for the treatment of IBS with diarrhea (IBS-D) in adult men and women.
In studies, eluxadoline was shown to reduce abdominal pain and improve stool consistency.
The drug was FDA approved in May 2015 

40. IBS with Constipation (IBS-C)
Lubiprostone
It helps to promote secretion through chloride channels in the bowel which in turn promote peristalsis, the coordinated muscle contractions that propel contents through the gastrointestinal (GI) tract.
This medication has been shown to be effective for treating constipation symptoms.
It is approved for use in women with constipation-predominant IBS (IBS-C), and in men and women with chronic constipation (without predominant abdominal pain).

41. IBS with Constipation (IBS-C)
Linaclotide 
It is a guanylate cyclase-C agonists.
Increases the motility of GI tract
Blocking pain signals in the intestines.
Recommended for IBS –C & CC
In studies, patients experienced improvement in pain or discomfort, bloating, and bowel function

42. How long to treat ? Relief of patient symptoms is the goal
Symptoms of IBS in majority are intermittent
Normally drugs are given for 2-4 months and repeated if relapse occurs
Always look out for Red Flag signs
5HT receptor drugs never used > 3 months continuously

43. Prognosis Relapses are common
9-10% develop organic disease a median of 15 years after diagnosis
Poor prognosis
Excessive psychological distress
Anxiety, long duration of complaints

44. Prognosis Relapses are common
9-10% develop organic disease a median of 15 years after diagnosis
Poor prognosis
Excessive psychological distress
Anxiety, long duration of complaints