Prof. Giovanni Barbara, Professor of Medicine and Gastroenterology at the University of Bologna, Italy: http://www.kiwifruitsymposium.org/presentations/functional-gastrointestinal-disorders-and-the-role-of-diet/ Roughly 30% of the population is affected by at least one of the several functional gastrointestinal disorders (FGIDs) with functional dyspepsia, irritable bowel syndrome (IBS) and chronic constipation (CC) being the most common.

1. Functional digestive disorders and the role of diet
Prof. Giovanni Barbara
University if Bologna, Italy

2. Functional digestive disorders
and the role of diet
Giovanni Barbara
Department of Medical and Surgical Sciences
Alma Mater Studiorum, University of Bologna, Italy
(1088 – 2016)

3. Up to 60% of the Population Reports GI Symptoms
Heartburn
Abdominal
pain /
bloating
Early satiety,
nausea
Constipation
Diarrhea
If you are symptom-free, you are in the minority!
Thompson WG et al. Dig Dis Sci 2002; 47:225

4. Burden of Gastrointestinal Disease
Peery AF et al., Gastroenterology 2012;143:1179–1187

5. Functional Gastro-Intestinal Disorders (FGID)
(Symptoms arising from the GI tract not explained by any detectable disease)
Gastro-Duodenal
• Functional dyspepsia
• Belching Disorders
• Nausea and Vomiting Disorders
Functional Bowel Disoders
• Irritable Bowel Syndrome
• Functional Constipation
• Functional Bloating
• Functional Diarrhea
• Functional Abdominal Pain
Ano-Recutum
• Functional Incontinence
• Functional Anorectal Pain
• Dischezia
Gallbladder/Sphincter of Oddi
• Functional galbladder disorder
• Functional SO disorder
Esophagus
• Functional heartburn
• Gastro-Esophageal Reflux
• Functional Dysphagia
• Globus
Drossman DA. Gastroenterology 2006;130:1377-90

6. The Common View of FGIDs
• The term ‘functional’ is often
improperly use to indicate an
‘idiopathic’ or ‘cryptogenetic’
condition
• Patients are labelled as ‘neurotic’,
‘apprehensive’, otherwise
healthy individuals with ‘an
imaginary disease’

7. IBS Definition (Rome III Criteria)
Recurrent abdominal pain or discomfort for at least
3 days per month, during the last 3 months associated
with at least 2 of the following symptoms:
Improvement with
bowel movement
Onset associated
with changes in
the frequency of
bowel movements
Onset associated
with changes in
the form of stool
Longstreth et al., Gastroenterology 2006;130:1480-91

8. World Prevalence of IBS is High
Pooled global prevalence = 11.2% (range: 1.1 - 45%)
Enck P et al., Nature Reviews Disease Primers 2016;2:1-24

9. Incidence of IBS
Jones et al., Aliment Pharmacol Ther 2006;24:879-86
Age (years)

10.  Move out, leave home
 Change diet
 Start a new job
 Start & end relationships
Why Young Adults?

11. Why women?

12. IBS Subtypes
Longstreth GF et al. Gastroenterology 2006;130:1480-91
Bristol Stool Form Scale
% BM
hard or
lumpy
% BM loose or watery
0
25
50
75
100
0 25 50 75 100
IBS-U
IBS-C IBS-M
IBS-D
25% of BM is the
threshold
for classification
Bristol
types 1
and 2
Bristol
types 1
and 6
Bristol
types 6

13. Correlation between Transit Time and BSS
O'Donnell et al Br Med J 1990;300:439-40
Colonic
Transit
Time
(h)
Bristol stool form score
1 2 3 4 5 6 7
80
40
0
Water contentFast

14. IBS Subgroups
 IBS-C: IBS with constipation; IBS-A: Alternating IBS; IBS-D: IBS with diarrhea
• 75% will experience exchange in subgroup over tim (more likely from IBS-A to IBS-C than to IBS-D
Talley NJ et al. Am J Epidemiol.1995; 142:76
Guilera M et al., Am J Gastroenterol 2005;100:1174-84
Ersryd A t al., Aliment Pharmacol Ther 2007;26:953-61
IBS-A
19-49%
IBS-D
15-36%
IBS-C
19-44%

15. Functional Constipation is Very Common
Rome II definition
 15% Canada
 14% Spain
 10% US
Longstreth et al., Gastroenterology 2006;130:1480-91

16. IBS-C and Functional Constipation Overlap
18%
Ford AC et al., Aliment Pharmacol Ther 2014;39:312-321
• Younger
• >Single
• >Female
• >Anxious
Pain No pain
Functional
Constipation
(n=513)
IBS-C
(n=173)

17. Impact of IBS on Quality of Life (SF-36)
0
10
20
30
40
50
60
70
80
90MeanScore
HC (n=1.412)
IBS (n=1.302)
IBD (n=546)
Heart failure (n=216)
Hahn BA et al., Digestion 1999;60:77-81
 Uso di risorse sanitarie
 Produttività lavorativa

18. Work Productivity (WPAI: IBS-C)
(European IBIS-C Study)
0
10
20
30
40
50
60
Italy France Germany Spain Sweden UK
Presenteism
Absenteism
Barbara et al., FISMAD 2015

19. Total costs of IBS-C (direct and indirect)
(European IBIS-C Study)
0 500 1000 1500 2000 2500 3000
Total direct and indirect costs
Direct costs (NHS)
Direct costs (Patient)
Indirect costs
€ / patient / 12 months
(mean ± 95% CI)
Barbara et al., FISMAD 2015

20. Mechanisms involved in irritable FGID
Psychosocial factors
Peripheral factors
Top – down
Bottom – up
Brain Gut Axis
IBS, irritable bowel syndrome

21. Colonic motor response to stress
Motility
3+
2+
1+
0
“Reassurance”
10 20 30 40
Time (min)
“Disease discovery”
Almy TP et al. Gastroenterology 1949;12:437-49

22. Intestinal Transit Times in IBS-C and FC
0
10
20
30
40
50
60
70
80
Small Bowel Total Colon Right Colon Left Colon Rectosigmoid
HC IBS-C FC
TransitTime(h)
* *
* * * *
Rao SSC et al., Neurogastroenterol Motil (2011) 23, 8–23

23. Visceral hypersensitivity in FGID
(decreased threshold for perception of stimuli)
Sensation  Discomfort  Pain
1 Richter J et al., Gastroenterology 1986;91:845-52
2 Tack J et al., Gastroenterology 2001;121:526-35
3 Mertz H et al., Gastroenterology 1995;109:40-52
4 Azpiroz F et al., Neurogastroenterol Motil 2007;19 (S1):62-88NCCP, non-cardiac chest pain
Normosensitive
Hypersensitive
50
0
%ofpatientswith
hypersensitivity
100
NCCP(1) FD(2) IBS(3,4)

24. IBS is a micro-organic disease
Barbara G et al. Gastroenterology, in press

25. What diet are you on?

26. IBS Patient’s Perception on the Efficacy of Treatments
82%
67%
45%
27%
5%
10%
27%
16%
9%
17%
23%
53%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Diet Drugs
(Prescription)
Drugs (OTC) Alternative
Therapies
Yes
No
Don't Know
Lacy BE et al., Aliment Pharmacol Ther 2007;25:1329-41

27. Perceived Food Intolerance in IBS
There is something wrong with food
84%
Böhn et al, Am J Gastro 2013; 108:634 – 641

29.  Management based on nature (IBS subtype) and severity of symptoms
 First line
• Dietary and lifestyle advice [eg, physical activity, low FODMAP, probiotics]: IBS
• Anti-spasmodics [eg, otilonium bromide]: IBS pain / bloating
• Laxatives [eg, PEG]: IBS-C
• Anti-diarrhoeals [loperamide]: IBS-C
 Second line
• Antidepressants [TCA or SSRIs]: IBS (pain / psychological impairment)
• Linaclotide [guanylate cyclase-C agonist]: IBS-C
• Lubiprostone [Cl- channel-2 agonist]: IBS-C
• Cholestiramine [bile acid sequestrant] if BAM suspected: IBS-D
• Rifaximin [non-absorbable antibiotic]: IBS-D / IBS-M
• Ondansetron / alosetron [5HT-3 antagonists]: IBS-D
Irritable Bowel Syndrome – NICE Guidance
Hookway C et al., Br Med J 2015;350

30. Simren M. Gastroenterology 2014;146:10-12
FODMAPS and IBS
Fermentable Oligo-, Di-, Mono-sAccharides and Polyols
= wheat, dairy, onions, celery and many processed foods

31. Halmos EP et al., Gastroenterology 2014;146:67-75
Low FODMAD vs. Standard Diet
Controlled Cross-Over Study in 30 IBS Patients
Overall
symptoms

32. Chages in Microbiota
with a Diet Low in FODMAPs
Halmos EP, et al. Gut 2015;64:93–100

33. What do you think you’re gonna eat then?

34. The Low FODMAP Diet Concept
• All foods with a high content of
FODMAPs are replaced with low-
FODMAP foods from the same
groups
• If the response is excellent, then
patients follow an individualized,
step-down food reintroduction plan to
determine their tolerance to specific
FODMAPs
Gibson et a., Gastroenterology 2015;148:1158-74
Fruit
Lactose
containing
foods
Vegetables
LOW FODMAP
High FODMAP
Food Category

35. 35
Benefits of dietary fibre in constipation
• Reduces intestinal transit
time
• Increases faecal mass
• Stool softening

36. Mechanisms of action
Eswaran et al 2013 Am J Gastroenterol
4g for every g dietary fibre

37. Tonini et al., Neuroscience 1996;73:287-97
Peristalsis and Related Neuronal Circuitries

38. Kiwifruit stimulates the growth
of beneficial colonic bacteria

39. Types of dietary fibre
Soluble and insoluble fibre often co-exist in intact plant cell walls
Short-chain Long-chain
Oligosaccharides
FOS, GOS
Resistant
starch
Pectin
Inulin
Guar gum
Psyllium
Ispaghula
Oats
Wheat bran
Lignin
Some fruit &
vegetables
Cellulose
Sterculia
Methylcellulose
Fermentability
    
Solubility
    

40. Effect of fibre on global symptom improvement
Bijkerk et al, Aliment Pharmacol Ther 2004;19:245
SOLUBLE FIBRE
INSOLUBLE FIBRE
Arthurs and Fielding, 1983
Jalihal and Kurian, 1999
Longstreth et al., 1981
Nigam et al., 1984
Prior and Whorwell, 1987
Toskes et al., 1993
Ritchie and Truelove, 1979
Ritchie and Truelove, 1980
Cook et al., 1990
Fowlie et al., 1992
Snook and Shepherd, 1994
Soltoft et al., 1976
Subtotal (95%CI) (56% pla vs 50% treatment)
Test for heterogeneity chi square=0.68; P=0.88
Test for overall effect z=-1.01; P=0.3
Subtotal (95%CI) (41% pla vs 64% treatment)
Test for heterogeneity chi square=13.44; P=0.062
Test for overall effect z=6.31; P<0.0001
Favours control Favours treatment
Total (95%CI) (45% pla vs 60% treatment)
Test for heterogeneity chi square=27.97; P=0.0033
Test for overall effect z=4.93; P<0.00001
-2-1 1 105

41. Response to fiber in patients with constipation
according to underlying mechanism
0
10
20
30
40
50
60
70
80
90
Slow Transit Disordered
defecation
No pathological
findings
%Responders
Voderholzer WA et al., Am J Gastroenterol 1997;92:95–8

42. Kiwifruit in IBS-C and CIC
Study Design
• Non-randomized, placebo (non double
dummy) controlled study
• Two kiwifruit daily intervention (Actinida
deliciosa)
• Two weeks run-in; four weeks
intervention; 1 week follow-up
• Fifty-four patients with IBS/C and 16
healthy adults
Asia Pac J Clin Nutr 2010;19 (4):451-457

43. Effect of Kiwifruit on Colonic Transit Time
0
10
20
30
40
50
60
HC IBS - Pla IBS - Kiwi
Before After
Colonictransit(hrs)
P=0.079 P=0.493 P=0.012
**
Asia Pac J Clin Nutr 2010;19 (4):451-457

44. Results - Bowel Habit & Fecal Volume
Bowel Habit Frequency Fecal Volume
Asia Pac J Clin Nutr 2010;19 (4):451-457

45. • An open, non-controlled and
non-randomized longitud
• 46 patients with constipation
(Rome III criteria).
• Weeks 1 and 2 no kiwifruit and
weeks 3-5 three kiwifruit per
day (Green kiwifruit, Actinidia
• deliciosa var Hayward)
Kiwifruit in IBS-C and Constipation
Study Design
Cunillera O et al., Rev Esp Nutr Hum Diet. 2015;19: 58-67

46. Bowel Habit Characteristics
Frequency Ease of defecation Fecal Volume
Day Day Day
Cunillera O et al., Rev Esp Nutr Hum Diet. 2015;19: 58-67