This document summarizes research on the diagnosis and treatment of irritable bowel syndrome (IBS). It begins by defining IBS and reviewing its prevalence in Italy. It then discusses the diagnostic criteria for IBS, emphasizing the importance of a symptom-based positive diagnosis. Various IBS subtypes and comorbidities are also outlined. Regarding treatment, the document examines dietary approaches including low FODMAP diets, the use of probiotics and antibiotics, and the importance of the patient-physician relationship. It stresses the multifactorial nature of IBS and need for multidimensional diagnosis and treatment.

1. Sindrome dell'intestino
irritabile: diagnosi e terapia
Relatore: Prof. E. Corazziari (Roma)

2. FGID: DEFINITION
“ Variable combination of chronic or
recurrent gastrointestinal symptoms
not explained by structural or
biochemical abnormalities”
Drossman et al Gastroenterol Int 1990;3:159

3. FUNCTIONAL BOWEL DISORDERS
ROME EVOLUTION
From the Irritable Colon Syndrome to
Functional Bowel Disorders
 Irritable Bowel Syndrome (Pain + Bowel Disorders)
 Functional Constipation (+/- Pain)
 Functional Diarrhea (no Pain)
 Functional Abdominal Bloating
 Unspecified bowel disorders

4. IBS PREVALENCE IN ITALY
FACE-FACE INTERVIEW
Physical Ex. & US
Random/Electoral Rolls
n=46,139 Resp. R 63,2%
IBS ROME I CRITERIA
F= 10.7%
M= 5.4%
E Corazziari et al. Digest and Liver Disease 2008;40:944-950 4

5. LA DIAGNOSI DI IBS

6. IBS- DIAGNOSTIC CRITERIA
HOW TO MAKE A DIAGNOSIS OF A
CHRONIC FUNCTIONAL DISORDER
WHEN NO BIOLOGICAL MARKER
EXISTS ?
 By exclusion
 Positive-Symptom based

7. IBS- DIAGNOSTIC CRITERIA
Exclusion of the Diseases with
Detectable Diagnostic Markers
 useful to detect relevant disorders in few patients
but
 it requires to submit many patients to many
investigations with elevated costs and risks of iatrogenic
damage
and
 it does not offer any certainty about the origin of
symptoms

8. IBS-DIAGNOSTIC CRITERIA
Positive symptom-based diagnosis
OFFER CONFIDENT DIAGNOSIS?
 Reduce unneeded investigations
 Plan treatment
 Strengthen patient compliance to
treatment and coping ability with chronic
suffering and daily limitations

9. IBS SUBGROUPS ACCORDING TO ROME
QUESTIONNAIRE AND DIARY CARD
IBS-D
47%
IBS-C
22%
23%
12%
12%
53%
40%
60%
N=68
K= 0.6
6%
75%
13%
6%
85%
6%
9%
IBS-D
IBS-C
IBS-M
IBS-U
Piacentino D et al DDW 2010

10. ABDOMINAL PAIN AND BLOATING DIFFER
IN RELATION TO EATING AND
DEFECATION IN IBS PATIENTS
Carboni S, Cantarini R, Badiali D, Pallotta N, Corazziari E. DDW 2007

11. TWO YEAR (IN)STABILITY OF ROME II IBS
Williams et al APT 2006; 23: 197-205
30%
IDENTICAL
IBS subtypes
ROME II
IBS
N= 697
18%
ABD PAIN
37%
BOWEL
45%
NO
SYMPTOMS
52%
NOT IBS
18% CHANGED
SUBTYPES
D
C
4% M
7%

12. IBS-C-CIC AND IBS-D-FD OVERLAP
Ford A.C. et al. Aliment Pharmacol Ther 2014;39:312-321

13. ONE YEAR (IN)STABILITY (%) OF ROME III
IBS-C & FC
Wong et al. Am J Gastroenterol 2010;105:2228
35.5
FC
WELL
IBS-M
WELL
IBS- C
14 25.5
39

14. BOWEL CHARACTERISTICS IN
IBS-C vs CIC
90
80
70
60
50
40
30
20
10
0
<3 ev/WK Hard Stools Straining Inc. Empty. Stool block Digital
IBS-C
CIC
%
* p<0.001
*
* * *
Ford AC et al. APT 2014;39:312-321
*
*

15. THE CONSTIPATION UNIVERSE
Rey E et al. Am J Gastroenterol advance online publication, 4 March 2014;doi:10.1038/ajg.2014.18

16. THE VANISHING FUNCTIONAL
ORGANIC BOUNDARIES
 Lactase deficiency
 Celiac disease
 Gluten sensitivity
 Bacterial overgrowth
 Bile salt malabsorption
Non specific minimal change inflammation
Subclinical intestinal inflammation

17. EXTRA-GI CONDITIONS IN DBF (>30%)
 URINARY
 Interstitial cystitis
 Incontinence
 Detrusor instability
 MUSCOLOSKELETAL
 Fibromyalgia
 Backache
 Headache
 SEXUAL
 Dyspareunia
 Decreased libido
 Inhibited orgasm
 PSYCHOLOGICAL
 Affective disorders
 Stress sensitivity
 Illness behavior
 Health seeking
behavior
Whorwell et al 1986; Nyhlin et al 1993; Triadofilopoulos et al 1991

18. COMORBIDITIES ASSOCIATED WITH IBS
COMORBIDITY REPORTED PREVALENCE IN IBS
GI disorders
Gastritis, duodenitis 31.2%
Inflammatory bowel disease 27.9%
Gastroesophageal reflux disease 19.0%
Dyspepsia 17.4%
Oesophagitis 15.5%
Anal disease 15.4%
Psychiatric disorders
Depression 30.5%
Stress reaction 17.2%
Anxiety state 15.5%
Symptom-based somatic diagnoses*
Chronic fatigue, malaise 20.1%
Fibromyositis (myalgia) 14.5%
Pelvic pain, *vulvodynia p<0.05
8.6%
Temporomandibular joint disorder 3.3%
Dysmenorrhoea 2.3%
Cystitis 1.8%
Whitehead WE et al. Am J Gastroenterol 2007;102:2762

19. STRESSFUL EVENTS
PREDICT
 Onset of FGIDs
 Symptom exacerbation and
health seeking
 IBS symptom intensity
Bennett EJ et al. Gut 1998: 43:256
Creed FH et al. Gut 1988; 29:235

20. PSYCHOPATHOLOGY IN
IBS DYSPEPSIA COMORBIDITY
Piacentino D et al. 2014 Submitted for publication

21. IBS SEVERITY
DETERMINED BY PATIENT’S SYMPTOM REPORT AND BEHAVIOR
COMPOSITE OF
 GI & EXTRA GI SYMPTOMS
 DEGREE OF DISABILITY
 ILLNESS-RELATED PERCEPTIONS
 ILLNESS-RELATED BEHAVIOR
 PSYCHOSOCIAL DISTRESS
 GENDER / AGE
Drossman DA et al. Am J Gastroenterol
2011;106:1759;doi:10.1038/ajg.2011.201;published online 12 July 2011

22. PSYCHOLOGICAL STATUS IN
IBS-C vs CIC & IBS-D vs FD
40
35
30
25
20
15
10
5
0
IBS-C
IBS-D
CIC
FD
ANXIETY SOMATIZATION
%
* p<0.00
*
*
*
*
Ford AC et al. APT 2014;39:312-321

23. THE MULTIDIMENSIONAL DIAGNOSIS OF IBS
Symptom-based diagnosis of IBS
 Diagnose IBS-Subtype
 Assess IBS severity
Assess Stress and Psychological Status
 Assess Gastrointestinal comorbidities
Assess extragastrointestinal comorbidities
And
Related polytherapy

24. CONSIDERAZIONI SULLA DIAGNOSI DI IBS
 I CRITERI DI ROMA
 Categorizzano a fini classificativi le grandi sindromi funzionali
 Non identificano tutti i sottotipi di pazienti
 IBS-C E STIPSI FUNZIONALE, IBS-D E DIARREA FUNZIONALE FANNO PARTE DI
UNO STESSO SPETTRO
 NELLA PRATICA
 IDENTIFICARE LE SOTTOSINDROMI
E
 AGGIUNGERE ALTRE VALENZE CLINICHE
 DIAGNOSI MULTI DIMENSIONALE
 LA SEVERITÀ DI IBS NON E’ MISURABILE SUI SINTOMO INTESTINALI, MA DA UN
COMPLESSO DI FATTORI.
 I FATTORI PSICOSOCIALI SONO FORTEMENTE ASSOCIATI ALLA SEVERITÀ DEL DOLORE
 NELLA PRATICA
NECESSITÀ DI SISTEMATIZZARE UN METODO SEMPLICE PER VALUTARE IL GRADO
E LE COMPONENTI DELLA SEVERITÀ

25. LA TERAPIA DELL’IBS

26. PSYCHOLOGICAL
IBS
•GENETIC
•DISEASES
•STRESSORS
PATIENT
BEHAVIOR
CNS
STATUS
GI
ENS
PHYSIOLOGY
PHYSICIAN
THERAPY

27. Doctor-Patient Relationship - FGIDs
What the Patient Hears
23
Just to be
sure . . .
You have
IBS . . .
Nothing to
worry
about . . .
Blah
Cancer
Blah
Blah

28. They
think it’s
all in my
head
IBS - Patient’s Agenda
My symptoms
are worse
Do I have
cancer?
I’m under
more stress
Why am I
not getting
better?
Will
you
believe
me?
Am I crazy?
25

29. IBS - Doctor’s Agenda
Serious
disease
Recent
life stress
Psychologic
comorbidity
Hidden
agenda
narcotics
disability
laxatives
Referral
elsewhere?
Social and
cultural
factors
What do
I do?
26

30. IBS - RELAZIONE MEDICO-PAZIENTE
Acquisire la fiducia di un paziente stigmatizzato e che non capisce
l’origine dei disturbi
• Capire la sofferenza
• Spiegare i disturbi
• Educare il paziente
• Indicare obiettivi possibili

32. STRENGTH OF DOCTOR-PATIENT
RELATIONSHIP
Owens et al Am Int Med 1995
Placebo Effect: 20-40%
Kathryn T et al. Plos One 2012;7;
e48135
Number of FU Visits for FBD
Genetics & Pl response
Cathecol-O-Methyltransferase Val 108 Met Polym.
PFC

33. PLACEBO RESPONSE IN IBD
Response %
UC 17-28
CD 18-36
CD Fistula closure* 16-18
Sands B Dig Dis 2009;27:68-75
* Ford AC et al Clin Gastroenterol Hepatol 2014 S1542-
3565(14)01315-9.doi 10,1016/j.cgh.2014

34. TREATMENTS FOR FBD
Bloating
 Diet
Abdominal pain/discomfort
Diet
Diarrhea
 Diet
Constipation
 Diet
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function

35. DIET IN IBS (EIGHT STUDIES)
Brandt LJ et al. American J Gastroenterol 2009;104 Suppl 1

36. FODMAP effects in the IBS patients

37. LOW-FODMAP STUDIES
Three studies report symptom improvement with low-FODMAP
diets in IBS patients
1. a significant number of IBS patients report gastrointestinal (GI)
Staudacher et al, 2011: retrospective
mmmmmmmmmmmmmmmmmmmmmsymptom foods containing
2. it has been hypothesized that gluten could act as a trigger for GI
De Roest et al, 2013: observational
symptoms IBS and other clinical conditions s
3. GS is characterized by GI and extra-GI symptoms in the absence of
Halmos et al, 2014:
the typical immunological and mucosal alterations caused by the
ingestion of gluten
- accurate control of nutrients
- 77% fructose malabsorption
- crossover with unblinding effect
(only 17% of IBS patients did not
symptoms in GS patients are similar to those of IBS patients, even
recognize the type of diet)
gluten hypersensitivity has been included among the possible
etiopathogenetic or exacerbating factors for IBS symptoms

38. EFFECTS OF LOW FODMAP DIET IN IBS A
DOUBLE BLIND PARALLEL CONTROLLED CLINICAL TRIAL
BLOATING
PAIN
Piacentino et al. DDW 2014

39. TREATMENTS FOR FBD
Constipation
 Fibers (Ispaghula/psyllium)
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function

40. BULK LAXATIVES
Evidence
Level
Recommendation
Grade
Bran 3 C
Methylcellulose 3 C
Psyllium 2 B
Psyllium+Senna* 3 C
Rankumar, Rao, AJGE 2005;
American College GE, AJGE 2005;
*Marlett et al AJGE, 1987
Aggravate Bloating, Dyspepsia, Bran Ineffective in Slow Rectal Transit,
*Aggravate Bloating & Cramps

41. TREATMENTS FOR FBD
Bloating
 Probiotics
Abodminal pain/discomfort
 Probiotics
Diarrhea
 Probiotics
Constipation
Probiotics
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function

42. FLOW DIAGRAM OF IDENTIFIED STUDIES FOR
META-ANALYSIS OF PROBIOTICS IN IBS
NNT=7
AC Ford et al. Am J Gastroenterol 29 July 2014;doi:10,1038/ajg.2014,202

43. LIMITS OF PROBIOTIC STUDIES
LITTLE NUMBER OF PROPERLY-PERFORMED STUDIES
META-ANALYSIS POOL STUDIES WITH
 Different Probiotics
 Different Probiotic Species Combination
 Different Dosages
 Different Conditions
 Different Patients
 Few Patients
Direct-to-consumer marketing and lack of regulation are
obstacles to proper clinical studies
43
VERNA E.C. ET AL. THER ADV GASTROENTEROL 2010;5:307-319

44. FBD TREATMENT
WITH PROBIOTICS
DIARRHEA
PAIN BLOATING
GONFIORE DIARREA
CONSTIPATION
BLOATING
GONFIORE
Lactobacillus GG
VSL #3
 Lactobacillus
Plantarum
Lactobacillus Reuterii
Bifidobacterium Infantis
Lactobacillus Casei
Saccharomyces Boulardii
B.Longum/Rhamnosus
Acidophilus
L. Casei/Paracasei
/Thermophilus
B. Lactis Animalis
L. Casei Shirota

45. TREATMENTS FOR IBS
Bloating
 Antibiotics
Diarrhea
 Antibiotics
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function

46. EFFECT OF RIFAXIMIN ON NON-CONSTIPATED
IBS
46
Pimentel M et al. N Engl J Med 2011;364:22-32

47. TREATMENTS FOR FBD
Abdominal pain/discomfort
 Antispasmodics
 Antidepressants
Abdominal
pain /
discomfort
Bloating / - TCAs/SSRIs/SNRIs
distention
Altered
bowel
function

48. ANTISPASMODICS IN IBS
Poynard T. et al . Aliment Pharmacol Ther 2001;15:355-361

49. ANTIDEPRESSIVI NELLA SII
ANTIDEPRESSIVI
Jackson JL et al A J Med 2000
Disordine dell’asse Cervello- Studi controllati
Visceri
Alterata motilità GI
Ipersensibilità viscerale
Alterazione dei
meccanismi centrali di
regolazione
Neuroendocrino
Autonomico
Cognitivo
della percezione del
dolore

50. EFFICACY OF ANTIDEPRESSANTS AND
PSYCHOLOGICAL THERAPIES IN IBS
NNT 95%CI
TCA 4 3-6
SSRI 4 2.5-20
CBT 3 2-6
Hypnot 4 3-8
Ford AC et al. AJG 2014;109:1350-65

51. ANTIDEPRESSANTS FOR IBS
CLINICAL CONSIDERATION
TCAs in IBS-D, SSRIs in IBS-C
SSRI/SNRI for anxiety
Poor response3 Satisfactory response3
 Switch to different class antidepressant
 Combine treatments as augmentation
 Obtain psychiatry consultation
 Continue at minimum effective dose for
6 to 12 months
 Long-term therapy may be warranted for
some patients
1. ACG Task Force on IBS. Am J Gastroenterol 2009;104(suppl 1):S1-S35
2. Ford AC et al. Gut 2009;58:367-378
3. Grover M. Drossman A. Curr Opin Pharmacol 2008;8:715-723

52. TREATMENTS FOR FBD
Constipation
Secretagogs Linaclotide
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function

53. T53
Chloride Channels in Intestinal Transport
Cl-
Cl-
CFTR
channel
Na+
K+
K+
2Cl K+
-
Tight
junction
H2O
Na+
H2O
Na+
Ion Transport
Na+
Enterocytes
Cl C2
channel

54. AZIONE DELLA LINACLOTIDE
SULL’EPITELIO INTESTINALE
Corsetti M, Tack J. UEG Journal 2013;1:7-20

55. EFFETTO DELLA LINACLOTIDE NELLA
IBS-C
Chey WD et al. AJG 2012;107:1702-12

56. EFFECT OF LINACLOTIDE
VS PLACEBO
IBS-C
290g
NNT
CC
145g
NNT
CSBM(3/WK) 8 7
Abd. Pain/Disc. 8 9
CSBM+Abd Pain 12 5
Adequate Relief (>75%) 5 4

57. TREATMENTS FOR FBD
Bloating
 Diet
 Probiotics
 Antibiotics
Abdominal pain/discomfort
Probiotics
Antispasmodics
 Antidepressants
- TCAs/SSRIs/SNRIs
Diarrhea
 Diet
 Probiotics
 Antibiotics
 Colestyramine
 Loperamide
Constipation
 Diet
 Fibers (Ispaghula/psyllium)
 Probiotics
 Linaclotide
Water-binding macrogol/Osmotic laxatives
 Prucalopride
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function Psychotherapy
CBT
Hypnotherapy

58. EFFECTIVENESS VS INVASIVENESS OF IBS TREATMENT
Less Effective More Effective
58
More Invasive
and/or Less Safe
Less Invasive
and/or Safer
Modified from Simrén M. et al Gut 2013;62:159-176
Linaclotide
Loperamide
Antibiotics
Probiotics
Loperamide
Prebiotics
TCA
Antispasm
Systematic
Exclusion Diets Low FODMAP DIET
Placebo

59. FMT IN REFRACTORY IBS (N=13)
%
Pinn et al. Presented at AM College Gastroenterology 2013

60. EFFECTIVENESS VS INVASIVENESS OF IBS
TREATMENT
Less Effective More Effective
60
More Invasive
and/or Less Safe
Less Invasive
and/or Safer
Modified from Simrén M. et al Gut 2013;62:159-176
Linaclotide
Loperamide
Antibiotics
Probiotics
Loperamide
Prebiotics
TCA
Antispasm
Systematic
Exclusion Diets Low FODMAP DIET
Placebo

61. APPROCCIO MULTIDIMENSIONALE AL PAZIENTE CON MALATTIA
CRONICA
 Stabilire una relazione terapeutica
• Valutare la storia medica, la personalità e la famiglia
 Valutare la qualità di vita e il livello di attività quotidiana
 Valutare la storia psicosociale
 Prescrivere test diagnostici
 Fare una diagnosi
• Spiegare e rassicurare
• Istituire terapia appropriata

62. GENETIC
IBS
DIETARY FACTORS
INFLAMMATION
HYPERSENSITIVITY
IMMUNE RESPONSE
STRESS
CNS/ENS ALTERATIONS
PSYCHOSOCIAL FACTORS
GI SECRETION
ALTERED MOTILITY
DYSBIOSIS
BEHAVIOR

63. IBS SEVERITY
DETERMINED BY PATIENT’S SYMPTOM REPORT AND BEHAVIOR
COMPOSITE OF
 GI & EXTRA GI SYMPTOMS
 DEGREE OF DISABILITY
 ILLNESS-RELATED PERCEPTIONS
 ILLNESS-RELATED BEHAVIOR
 PSYCHOSOCIAL DISTRESS
 GENDERE / AGE
Drossman DA et al. Am J Gastroenterol
2011;106:1759;doi:10.1038/ajg.2011.201;published online 12 July 2011

64. CO MORBIDITY
SYMPTOM
SEVERITY
EPISODE
FREQUENCY IBS
QOL

65. MULTIDIMENSIONAL DIAGNOSTIC ASSESSMENT OF IBS PATIENT
COMORBIDITY
BILE AC. MALABSORPTION
DIETARY FACTORS
HYPERSENSITIVITY
ENVIRONMENTAL FACTORS
RAPID TRANSIT
POLY THERAPY
LOPERAMIDE, TCA
FIBER, LINACLOTIDE
LAXATIVES, PRUCALOPRIDE
SPASMOLYTICS
COGNITIVE BEHAVIORAL TH
STRESS
PSYCHOLOGICAL ALTERATIONS
SLOW TRANSIT
SPASM
DYSBIOSIS
S
ILLNESS BEHAVIOR
IBS
Pain Severity
Episode Frequency
Episode Duration
QoL
COLESTYRAMINE
PROPER DIET
TCA 5HT3 ANTAGONIST
RELAXATION TRAINING HYPNOSIS
SSRI SNRI PSYCHOTHERAPY
PROBIOTICS ANTIBIOTICS

66. LONG DURATION
HIGH
SYMPTOM
SEVERITY
LOW
CONTINUOUS
INTERMITTENT
SHORT DURATION
HIGH
FREQUENCY
LOW
IBS
EPISODE
REASSURANCE ON DEMAND

67. CONSIDERAZIONI SULLA TERAPIA DI IBS
 LE TERAPIA FARMACOLOGICHE SONO STATE TESTATE SU IBS, IBS-C E IBS-D.
MANCANO STUDI SULLE SOTTOSINDROMI
 FONDAMENTALE IL RAPPORTO MEDICO-PAZIENTE E L’EFFETTO PLACEBO
 NELLA PRATICA
ESALTARE LE CAPACITÀ DEL MEDICO
 LA DIETA LOW-FODMAP OFFRE NOTEVOLE BENEFICIO
 LA LINACLOTIDE, PRIMO FARMACO CHE AGISCE TOPICAMENTE SULL’EPITELIO
SIA SU STIPSI CHE DOLORE
 NELLA PRATICA
IDENTIFICARE CHI RISPONDE ALLA DIETA LOW-FODMAP E ALLA LINACLOTIDE