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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)

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Alastair ForbesNorwich Medical School

Fibre in Gastroenterology

Is there anything new to say?

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Cocoa

Theobroma cacoa

Drink of Gods (Xocoatl)

theo = God

broma = drinkMexico (Maya, Incas, Aztecs)

Aphrodisiac

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Norwich

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Resistant carbohydrate Not digested by human enzymes

Poorly absorbed

Poorly metabolised

2 main groups

Fibre an introduction

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Polysaccharides with alpha (1,4)glycosidic bonds can be digested by the

small intestine

Polysaccharides with beta (1,4)

glycosidic bonds cannot


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Predominantly non-starch polysaccharides Also oligosaccharides and lignin

(polyphenols)

Mostly have structural roles in plants


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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

Specific fibres some examples

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Insoluble and soluble fibre

Physical and metabolic differences Water-holding capacity

Viscosity Solubility

Fermentability

Prebiotic capacity

Binding capacity

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Dietary fibre properties also affected by

Ripeness of food (eg fruit)

Preparation

raw vs cooked

whole vs grated

etc

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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 water-holding

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Water-solubility affects proportion that

reaches colon in health Some fibres form gels (eg pectin, guar)

Viscous gels important in delayingabsorption

Lower the glycaemic and hyper-cholesterolaemic effects of foods

Fibre solubility/viscosity

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Property mainly of soluble fibre Essential for colonic health

Only source of essential short chain fattyacids

Fibre fementability

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Saccharolytic fermentation dominates

and especially so in proximal colon Proteolytic fermentation more distal

(when most fermentable substratesexhausted)

Putrefaction (anaerobic metabolism of

peptides) also occurs yielding SCFAs

and ammonia, thiols, indoles, etc

Fibre fermentability

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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 fermentability

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~5% of energy needs in health

Main energy source for colonocytes Promote absorption of salt and water

Stimulate mucosal proliferation Increase mucus production

mucosal blood flow & oxygen uptake

Maintain mucosal integrity

Fibre SCFAs

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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

Butyrate

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RCT of whole grain fibre

End-point = urinary markers of proteincatabolism

Short-term study but impressive results Potential clinical value ?

Ross 2013

Fibre is anabolic ?

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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, Lactobacilliand Bifidobacteria

Clinical data largely supportive

Prebiotic effects of fibre

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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 bacteriamay be valuable

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Fibre and satiety/appetite control

Delays gastric emptying

Increases viscosity of gastric content Probable hormonal effects in small bowel

Fruit, fibre foods and supplements reduceappetite in the short-term

Visholm 2014

Meta-analysis confirms (minor) weight loss

Camilleri 2010

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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

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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 glycaemia

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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 mechanismsremain unclear

Viscous fibre and blood lipids

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Transit normalised if abnormal

Frequency increased by 1.4x per week if

constipation

Mainly bulk/water effect from insoluble fibre

Diarrhoea ameliorated and durationshortened (acute in children & antibiotic-

associated) Enteral tube feed-associated diarrhoea

improvedElia 2008

Fibre and the gut

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Dietary guidance & evaluation in IBS: n=46

Review at 3-6 months Advice was not just increased fibre

Patients increased dairy and vitaminintakes with decrease in FODMAPs

Overall symptom score and QoL improved

No correlation with any food group!

Mazzawi 2013

Fibre and IBS

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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 IBS

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Common and responsible for considerable

morbidity from complicaions Because of low fibre Western diet

Fibre and diverticula

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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 diverticula

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Relatively few reliable human data

Animal models show benefit in severalforms 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 inflammation

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New prospective study in IBD pathogenesis

Nurses Health Study n=170,776

269 incident CD, 338 UC compared to mean

Fibre and IBD

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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 IBD

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Not relevant after diagnosis

Evidence for protection from cereal fibre

still controversial .

No benefit from insoluble dietary fibre (FDA2000)

Clear benefit from all fibre (EPIC 2003)

Fibre and colon cancer

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Confusion perhaps because of typical

difficulties of interpreting diet in aetiology Or other factors?


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Confusion perhaps because of typical

difficulties of interpreting diet in aetiology Or other factors?

Difference between dietary andsupplementary fibre

Host genome

Dietary co-factors


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Type of fibre - EPIC database

Plasma alkyl resorcinol reflects wholegrainintake (wheat and rye)

Higher in North European populations thanMediterranean

Unclear how to interpret

Kyro 2014


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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


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>1000 mg/day yielded ORof 0.54

CI: 0.35-0.83 Effect modified by dietary fibre

Cancer risk reduced with increasinglevels of dietary calcium and fibre

intake to more than additive extent

Galas 2013


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Meta-analysis of almost 11000 patients

Summary relative risk of high vs low fibreintake = 0.72 (CI 0.63-0.83)

Stronger effect in case-control than incohort studies (RR 0.66 vs 0.92)

Effect strongest for cereal fibre and least

for vegetable fibreBen 2014

Fibre and colonic adenomas

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Interventional study of family members

Supplementary fibre

No apparent effect on cancer risk

Mathers 2012

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Fibre in HNPCC / Lynch

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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


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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 processedmeat yield OR of 1.3 and 1.4

But GG genotype has no link OR 1.03

Figueiredo 2014


Fib l i li t d

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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 a10g/d dietary supplementation

Zhang 2013

Fibre also implicated

in gastric cancer

Fib l i li t d

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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 also implicated

in pancreatic cancer

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Fibre in artificial feeding

Historically, commercially prepared feeds

were without fibre and the addition of fibrewas special

Increasingly fibre-containing feeds areconsidered the default typically 5-10g/L

Is this correct and safe?

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Indicated if constipation or diarrhoea Confirmation of value is stronger for

patients with diarrhoea than it is for

patients with constipationRabenek 1997

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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

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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

Fibre what next?

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forbes 2014

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