This deck describes why grains may cause bowel symptoms in people with sensitive bowel. It's not only about gluten, but FODMAPs and even bran.

1. Grains and gastrointestinal
symptoms
[Updated May 2015]
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2. Background
• There are myriad blog posts and “expert” opinions on gluten
and on its possible detrimental role in non-celiac disorders
• In these opinions the role of fermentable carbohydrates
(FODMAPs) and insoluble bran is sometimes dismissed
• On the other, medical doctors and even gastroenterologists
have been slow and reluctant to recognise the role of gluten or
grains per se in non-celiac disorders
• What does the evidence say about grains and gastrointestinal
symptoms?
2

3. Prevalence of non-celiac ”gluten
sensitivity”
• According to a systematic review prevalence is 0,5-13 %.
Higher figures are based on very selective populations
• Prevalence figures are often based on self-reports, expert
examinations and are always symptom based. NO biomarker
exists for gluten sensitivity
• It seems gluten free diet has not resolved symptoms in most
people with sensitive stomach, because according data from
UK:
– 42% of IBS patients considered themselves gluten sensitive but only 11,9 %
followed gluten free diet
– 28% of IBD patients consider themselves as gluten sensitive but only 6,2 %
followed gluten free diet
Molina-Infante J1, Santolaria S, Sanders DS, Fernández-Bañares F. Systematic review: noncoeliac gluten
sensitivity. Aliment Pharmacol Ther. 2015 May;41(9):807-20. Aziz I, et al.
A Study Evaluating the Bidirectional Relationship Between Inflammatory Bowel Disease and Self-reported
Non-celiac Gluten Sensitivity. Inflamm Bowel Dis. 2015 Apr;21(4):847-53.

4. Gastrointestinal symptoms can be
caused by at least 3 factors of gluten
containing grains
• Fermentable carbohydrates ,
ie. FODMAPs are shown to
cause gastrointestinal
symptoms in irritable bowel
syndrome
• Wheat bran can cause bloating
and pain in irritable bowel
syndrome (even if helps in
constipation)
• Gluten can cause symptoms in
a fragment of patients. Non-
celiac gluten sensitivity is
recognised as own disease
entity
4

5. 1. Fermentable carbohydrates
cause bowel symptoms
The FODMAP story
5

6. FODMAP*
Galactans
Oligosaccharides
Inulin GOS*
RaffinoseFructans
FOS*
Disaccharides
Lactose
Monosaccharides
Fructose Polyols
Isomalt
Maltitol
Lactitol
Xylitol
(Lactulose) Mannitol
*) FOS= Fructo-oligosaccharide
*) GOS= Galacto-oligosaccharide
Sorbitol
FODMAP: Fermentable
oligosaccharides, disaccharides,
monosaccharides and polyols
Jacqueline S. Barrett and Peter R. Gibson Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and
nonallergic food intolerance: FODMAPs or food chemicals? Ther Adv Gastroenterol(2012) 0(0) 1–8

7. Fermentable carbohydrates, 2 classes
FODMAPs
• Some of fermentable
carbohydrates (inulin, fructo-
oligosaccharides and galacto-
oligosaccharides) can be
classified as soluble fiber
• Poorly absorbed short chain
carbohydrates undergo rapid
and extensive fermentation in
colon which causes bloating,
gas formation, water retention,
urge to defecate and diarrhea
(or constipation in some
cases)
Non-FODMAPs
• Poorly absorbed
carbohydrates with longer
chains are less likely to cause
extensive symptoms because
they undergo slower and
incomplete fermentation (still
can cause minor symptoms)
– Resistant starch, beta-glucan,
pectin, gums & polydextrose

8. FODMAPs are proven cause of GI
symptoms in irritable bowel syndrome
*) RCT=Randomized controlled trials, non-RCT= Controlled trial, no randomization
↓↓↓=reduction ↑↑↑=increase
Staudacher H, Irving P, Lomer M, Whelan K. Mechanisms and efficacy of dietary FODMAP
restriction in IBS. Nat Rev Gastroenterol Hepatol. 2014 Apr;11(4):256-66.
RCTs* Non-RCT* Retrospective
cohorts/case-
control studies
↓↓↓ in some
symptoms
3 studies 1 study 6 studies
No difference in
any symptom
None of the
studies
None of the
studies
None of the
studies
↑↑↑in some
symptoms
None of the
studies
None of the
studies
None of the
studies
Effect of low-FODMAP diet on symptoms if IBS

9. Main sources of FODMAPs
Jacqueline S. Barrett and Peter R. Gibson
Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance:
FODMAPs or food chemicals? Ther Adv Gastroenterol(2012) 0(0) 1–8

10. In US wheat is a key source of inulin
and FOS
• Oligosaccharides inulin and
FOS are major causes of GI
symptoms in irritable bowel
syndrome
• Wheat is a key source of
fructans in American and
Western diets
10
Moshfegh AJ et al. Presence of Inulin and
Oligofructose in the Diets of Americans. J.
Nutr. 129: 1407S–1411S, 1999
Intake of FOS & inulin

11. 2. Wheat bran may cause GI
symptoms in persons with
sensitive bowel
Insoluble fiber, such as cellulose in bran can
cause bowel symptoms.
Wheat and rye brans are are also high in
FODMAPs
www.pronutritionist.net11

12. Wheat bran causes symptoms
• In an American randomized trial wheat bran increased abdominal
bloating (30 g/d) and did not ease any IBS-related symptom
• In a German randomized trial psyllium (10 g/d) relived bloating ,where
as wheat bran (21 g/d) worsened bloating in two weeks’ follow up
• 12 g grams of wheat bran daily was equally effective as placebo in
global score of IBS symptoms but increased wind and bloating in a 4
week randomized trial
• Not all randomized trials have shown deleterious effects in sensitive
bowel
12
Hebden JM et al. Abnormalities of GI transit in bloated irritable bowel syndrome: effect of bran on transit and symptoms.
Am J Gastroenterol. 2002 Sep;97(9):2315-20.
Effectiveness of plantago seed husks in comparison with wheat brain on stool frequency and manifestations of irritable
colon syndrome with constipation. Med Klin (Munich). 1994 Dec 15;89(12):645-51.
Hotz J, Plein K.Snook J, Shepherd HA. Bran supplementation in the treatment of irritable bowel syndrome. Aliment
Pharmacol Ther. 1994 Oct;8(5):511-4.

13. Wheat and rye brans are also rich
sources of inulin and fructo-
oligosaccharide (=fructans)
• Wheat, barley and especially
rye are rich in fructans
(FODMAPs) but oats is low
• Wheat is also rich in cellulose
and and lignin, insoluble fiber
components
13
Fructans = inulin and fructo-oligosaccharide (FOS)
Frølich W, Aman P, Tetens I. Whole grain foods and health – a Scandinavian perspective. Food Nutr Res.
2013;57

14. 3. Gluten in wheat and other
grains may cause symptoms. Or
may not.
If low-FODMAP diet is not followed, gluten or
wheat pills have caused symptoms in very
selected patients (2 Italian & 1 Australian
study)
If low-FODMAP diet was followed, gluten pills
did not cause more symptoms than whey
protein (1 Australian study)
14

15. Gluten caused bowel symptoms in a
highly selected population (no
FODMAP restrictions at the same time)
• A highly selective sample of
patients with subjective feeling
of gluten intolerance was
exposed to blinded gluten
challenge
• 60 % of patients reported
improvement in symptoms
• Symptoms didn’t improve in 32
% patients
• The test was done on purified
gluten (no extra FODMAPs
and bran on top of gluten)
www.pronutritionist.net15
Biesiekierski et al. Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized
Placebo-Controlled Trial. Am J Gastroenterol. 2011 Mar;106(3):508-14

16. Later study from the same
investigators: gluten caused no
symptoms when low-FODMAP diet was
followed at the same time
• When IBS patients with self-
reported gluten sensitivity
were re-challenged with gluten
pills they experienced no more
(any) symptoms than on
placebo
• The study differs from the
previous study in that the
participants followed low
FODMAP diet at the time of re-
challenge
16
Biesiekierski J et al. Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary
Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates. Gastroenterology 2013; 145, 320–328.

17. Wheat challenge in a highly selected
population
• 30 % IBS patients with subjective
wheat sensitivity actually show
wheat sensitivity in blinded wheat
challenge test (12 g/d)
• In those who proved to be wheat
intolerant, a dramatic increase in
pain, bloating and stool
consistency was observed during
wheat period
• Bran and FODMAPs may
contribute to symptoms as they
were not controlled in this trial
www.pronutritionist.net17
Changes in symptom severity over baseline during the double-
blind placebo-controlled wheat challenge: 2 weeks on wheat-
containing diet and 2 weeks on placebo.
Carroccio A et al. Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind
Placebo-Controlled Challenge: Exploring a New Clinical Entity, Am J
Gastroenterol. 2012 Jul 24. doi: 10.1038/ajg.2012.236.

18. Gluten caused some bowel and other
symptoms in a highly selected
population (no FODMAP restrictions at
the same time) • One week gluten free run-in period. Gluten
free diet was continued for further one week
(actual test period)
• Treatments: gluten pills 4.375 g/d vs placebo
pills, rice starch 4.375 g/d
• There was small but statistically significant
difference in bloating, abdominal pain, foggy
mind, depression, aphthous stomatitis
favoring placebo
• ” However, when we examined the individual
patients’ overall scores we found that only a
minority of the participants experienced a
real worsening of symptoms under gluten”
18
Di Sabatino A, et al. Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A
Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Clin Gastroenterol Hepatol. 2015 Feb 19.
pii: S1542-3565(15)00153-6.
N=59, cross over, 7 day-intervention

19. Gluten free diet reduces bowel movements
(BM) in people with sensitive stomach and
diarrhoea (IBS-D). Both intake of FODMAPs
and gluten are reduced when gluten free diet
is followed
19
Vazquez-Roque MI, et al. . Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in
irritable bowel syndrome with diarrhea. Am J Physiol Gastrointest Liver Physiol. 2012 Dec 1;303(11):G1262
• Both diets seemed to reduce
bowel movements but there
were significantly less bowel
movements (diarrhoea) during
gluten free diet (GFD)
• No other symptoms were
monitored!
• Permeability of small intestine
was reduced during GD

20. 4. Perhaps it’s the 3rd
factor: α-
amylase-trypsin inhibitors
20

21. Preliminary data from animal and in
vitro studies: α-amylase-trypsin
inhibitors are pro-inflammatory at level
of intestinal epithelium
21
Junker Y et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of
toll-like receptor 4. Journal of Experimental Medicine 2012; 209:2395-408
• “In this study, we show that members of the nongluten α-
amylase/trypsin inhibitor (ATI) family contained in wheat and
related cereals are strong inducers of innate immune
responses in human and murine macrophages, monocytes,
and DCs. ATI family members activate the TLR4–MD2–CD14
complex and elicit strong innate immune effects not only in vitro
but also in vivo after oral or systemic challenge.
• Our findings have broad implications not only for celiac disease
but also for other intestinal inflammatory disorders of the
gastrointestinal tract”

22. Conclusions
• FODMAPs, present abundantly in grains, do cause gastro-
intestinal symptoms in patients with sensitive stomach (irritable
bowel syndrome).
• Wheat bran may cause bloating and pain in some occasions
• Gluten can cause bowel symptoms in a fragment of patients, but
its role in triggering symptoms is still highly controversial
• Role of α-amylase/trypsin inhibitors is fully open because no
randomized trials/clinical studies are available
• Oats is more or less devoid of FODMAPs and gluten, and is
therefore better tolerated
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23. Top 3 readings
• Jacqueline S. Barrett and Peter R. Gibson Fermentable
oligosaccharides, disaccharides, monosaccharides and
polyols (FODMAPs) and nonallergic food intolerance:
FODMAPs or food chemicals? Ther Adv Gastroenterol (2012)
0(0) 1–8, open access
• Grabitske H & Slavin J. Low-Digestible Carbohydrates in
Practice. J Am Diet Assoc. 2008;108:1677-1681
• Sapone et al. Proposed new nomenclature and classification
of gluten-related disorders. BMC Medicine 2012, 10:13
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24. Welcome aboard
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http://www.pronutritionistblog.com
http://www.pronutritionist.net
Reijo Laatikainen, Authorized Nutritionist, MBA,
Dietitian
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