ESPEN Congress Geneva 2014

DISEASES ACROSS BORDERS: THE CASE OF IRRITABLE BOWEL

SYNDROME

Fibre in gastroenterology: is there anything new to say?

A. Forbes (UK)

Fibre in Gastroenterology
Is there anything new to say?
Alastair Forbes
Norwich Medical School

Cocoa

Theobroma cacoa
Drink of Gods (Xocoatl)
theo = God
broma = drink
Mexico (Maya, Incas, Aztecs)
Aphrodisiac

Norwich

Fibre an introduction

Resistant carbohydrate
Not digested by human enzymes
Poorly absorbed
Poorly metabolised
2 main groups

Fibre an introduction
Polysaccharides with alpha (1,4)
glycosidic bonds can be digested by the
small intestine
Polysaccharides with beta (1,4)
glycosidic bonds cannot

Fibre an introduction
Predominantly non-starch polysaccharides
Also oligosaccharides and lignin
(polyphenols)
Mostly have structural roles in plants

Specific fibres some examples

Cellulose beta (1,4) glucopyranoside

Hemicelluloses various sugar monomers
Pectin galacturonate & some rhamnose
Mucilage plant gums
Lignin highly branched phenylpropanoid
units
Oligosaccharides various monomer units
Inulin beta (2,1) linked fructose polymer
Resistant starch functional definition

Fibre an introduction
Insoluble and soluble fibre
Physical and metabolic differences
Water-holding capacity
Viscosity
Solubility
Fermentability
Prebiotic capacity
Binding capacity

Fibre an introduction
Dietary fibre properties also affected by
Ripeness of food (eg fruit)
Preparation
raw vs cooked
whole vs grated

etc

10

Fibre water-holding
Determined by physicochemical
properties
Higher in non-soluble fibre
Effect on stool mass
Influenced also by effects on flora as
bacteria contribute to stool water content

Fibre solubility/viscosity
Water-solubility affects proportion that
reaches colon in health
Some fibres form gels (eg pectin, guar)
Viscous gels important in delaying
absorption
Lower the glycaemic and hypercholesterolaemic effects of foods

Fibre fementability
Property mainly of soluble fibre
Essential for colonic health
Only source of essential short chain fatty
acids

Fibre fermentability
Saccharolytic fermentation dominates
and especially so in proximal colon
Proteolytic fermentation more distal
(when most fermentable substrates
exhausted)
Putrefaction (anaerobic metabolism of
peptides) also occurs yielding SCFAs
and ammonia, thiols, indoles, etc

Fibre fermentability
Saccharolytic fermentation mainly yields
SCFAs, lactate, H2 and CO2
Butyrate 15%
Propionate 25%
Acetate 60%

All are rapidly absorbed

Provide ~5% of energy needs in health

Fibre SCFAs
~5% of energy needs in health
Main energy source for colonocytes
Promote absorption of salt and water
Stimulate mucosal proliferation
Increase mucus production
wmucosal blood flow & oxygen uptake
Maintain mucosal integrity

Butyrate

Most important and most active SCFA

Increases MUC2 and mucus production
Promotes cell differentiation
Decreases paracellular permeability
Enhances ICAM-1, enteroglucagon

Direct anti-inflammatory effects

TNF, IL6, IL8, IFN, COX-2, NFB

Fibre is anabolic ?
RCT of whole grain fibre
End-point = urinary markers of protein
catabolism
Short-term study but impressive results
Potential clinical value ?
Ross 2013

Prebiotic effects of fibre

Concept parallel to probiotic
Specific non-digestible carbohydrates
growth of bacteria with health benefits
Highest butyrate production is from
fructose oligosaccharide and inulin
pathogenic G+ve and G-ve bacteria
Major effects on Clostridium, Lactobacilli
and Bifidobacteria
Clinical data largely supportive

Absorptive and binding effects of fibre

Fibre is ion binding
Historically thought to pose risk of
inhibition of absorption of key minerals
Recent evidence suggests the opposite
Calcium uptake and BMD increased by
fibre in adolescents
Binding of bile salts and some bacteria
may be valuable
20

Fibre and satiety/appetite control

Delays gastric emptying

Increases viscosity of gastric content
Probable hormonal effects in small bowel
Fruit, fibre foods and supplements reduce
appetite in the short-term
Visholm 2014

Meta-analysis confirms (minor) weight loss

Camilleri 2010

Viscous fibre and glycaemia

Benefit from delayed gastric emptying
Slower small bowel transit
Less glucose transport through unstirred
layer
Reduced access of amylase to dietary
starch
Lower postprandial glucose level (AUC)

Viscous fibre and glycaemia

In combination reduce post-prandial
glucose and increase insulin sensitivity
Especially guar, pectin, -glucan
Improve diabetic control
Probably non-fermentable fibre reduces
risk of diabetes
eg Fujii 2013, Yu 2014

Viscous fibre and blood lipids

Lowers LDL (no effect on other lipids)

No effects from non-soluble fibre
Attributed in part to effect on bile salts
Small effect
Bigger overall influence on CVS morbidity
from insoluble fibre but mechanisms
remain unclear

Fibre and the gut

Transit normalised if abnormal
Frequency increased by 1.4x per week if
constipation
Mainly bulk/water effect from insoluble fibre

Diarrhoea ameliorated and duration

shortened (acute in children & antibioticassociated)
Enteral tube feed-associated diarrhoea
improved
Elia 2008

Fibre and IBS

Dietary guidance & evaluation in IBS: n=46

Review at 3-6 months
Advice was not just increased fibre
Patients increased dairy and vitamin
intakes with decrease in FODMAPs
Overall symptom score and QoL improved
No correlation with any food group!
Mazzawi 2013

Fibre and IBS

Systematic review and meta-analysis
Comparisons with placebo, control or
usual management; n = 906
Significant overall benefit: RR = 0.86
CI 0.80-0.94; NNT =10

Effect from soluble fibre: RR = 0.83

No significant effect from bran: RR = 0.9
Unclear if effect limited to IBS subgroups
Moayyedi 2014 Epub

Fibre and diverticula

Common and responsible for considerable
morbidity from complicaions
Because of low fibre Western diet

Fibre and diverticula

Common and responsible for considerable
morbidity from complications
Not because of low fibre Western diet
No protection against diverticulosis
Association with diverticulitis also
questioned
Risk from seeds/nuts once diverticulosis
present also not supported by data
Peery 2013

Fibre and inflammation

Relatively few reliable human data
Animal models show benefit in several
forms of colitis
Butyrate probably effective in human colitis
Plantago ovata not helpful in preventing
relapse of ulcerative colitis
Hallert 2003, Vernia 2003, Fernandez-Banares 1994

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Fibre and IBD

New prospective study in IBD pathogenesis
Nurses Health Study n=170,776
269 incident CD, 338 UC compared to mean

Fibre and IBD

New prospective study in IBD pathogenesis

Nurses Health Study n=170,776
269 incident CD, 338 UC compared to mean
Intake of highest quintile of fibre (24.3g/d)
associated with 40% reduction in risk of CD
HR 0.59: CI 0.39-0.90

Most of benefit from fruit fibre

Little influence of fibre on UC incidence
HR 0.82 (NS)
Ananthakrishnan 2013

Fibre and colon cancer

Not relevant after diagnosis
Evidence for protection from cereal fibre
still controversial .
No benefit from insoluble dietary fibre (FDA
2000)
Clear benefit from all fibre (EPIC 2003)

Fibre and colon cancer

Confusion perhaps because of typical
difficulties of interpreting diet in aetiology
Or other factors?

Fibre and colon cancer

Confusion perhaps because of typical
difficulties of interpreting diet in aetiology
Or other factors?
Difference between dietary and
supplementary fibre
Host genome
Dietary co-factors

Fibre and colon cancer

Type of fibre - EPIC database
Plasma alkyl resorcinol reflects wholegrain
intake (wheat and rye)
Higher in North European populations than
Mediterranean
Unclear how to interpret
Kyro 2014

Fibre and colon cancer

Calcium also important thought to be
protective - but possibly a fibre effect
Case-control study of 1556 (703 vs 853)
incident cases using 148-item Food
Frequency Questionnaire
Higher consumption of calcium associated
with lower colon cancer risk
OR=0.93 (CI: 0.89-0.98) for every extra
100 mg Ca/day
Galas 2013

Fibre and colon cancer

>1000 mg/day yielded ORof 0.54
CI: 0.35-0.83
Effect modified by dietary fibre
Cancer risk reduced with increasing
levels of dietary calcium and fibre
intake to more than additive extent
Galas 2013

Fibre and colonic adenomas

Meta-analysis of almost 11000 patients
Summary relative risk of high vs low fibre
intake = 0.72 (CI 0.63-0.83)
Stronger effect in case-control than in
cohort studies (RR 0.66 vs 0.92)
Effect strongest for cereal fibre and least
for vegetable fibre
Ben 2014

Fibre in HNPCC / Lynch

Interventional study of family members
Supplementary fibre
No apparent effect on cancer risk
Mathers 2012

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Fibre and colon cancer

Genome-wide diet-gene interactions
Diet and ~2.7m genetic variants studied in
>9000 cases and >9000 controls
Red and processed meat intake more
common in cases; fruit / vegetable / fibre less

Fibre and colon cancer

Genome-wide diet-gene interactions
Diet and ~2.7m genetic variants studied in
>9000 cases and >9000 controls
Red and processed meat intake more
common in cases; fruit / vegetable / fibre less
2 specific polymorphisms of rs4143094 (on
10p) (TG and TT) plus dietary processed
meat yield OR of 1.3 and 1.4
But GG genotype has no link OR 1.03
Figueiredo 2014

Fibre also implicated

in gastric cancer

Meta-analysis of >580,000 cases

Highest vs lowest fibre intakes compared
Retrospective and much heterogeneity
Overall protective effect OR 0.58
Different types of fibre not analysable
Equivalent to a 44% reduction in risk for a
10g/d dietary supplementation
Zhang 2013

Fibre also implicated

in pancreatic cancer
Dietary analyses in case-control study of
326 vs 652 controls
4 dietary patterns identified
Those with the fibre and vitamin diet had
the lowest rate of pancreatic cancer
OR 0.55 (CI 0.36-0.86)
While the red meat diet doubles the risk
Bosetti 2013

Fibre in artificial feeding

Historically, commercially prepared feeds
were without fibre and the addition of fibre
was special
Increasingly fibre-containing feeds are
considered the default typically 5-10g/L
Is this correct and safe?

Fibre in artificial feeding

Indicated if constipation or diarrhoea
Confirmation of value is stronger for
patients with diarrhoea than it is for
patients with constipation
Rabenek 1997

Fibre in artificial feeding

Contra-indicated in some GI conditions
Intestinal strictures questionable
Abdominal compartment syndrome but
enteral feeding contra-indicated too
Acute pancreatitis ? (Besselink 2008)
Gastroparesis ?
Short bowel syndrome ?
Poor appetite ??
No evidence against in most conditions

Fibre what next?

Clear recommendations for boosting fibre
intake in the general population
Benefits of certain or probable extent
GI health, CVS, diabetes, cancer, etc
Soluble and insoluble fibres yield
complementary actions
No evidence for harm
Should be default for artificial feeding