The implications of Gut Health - Why the Food Supply Chain needs a concerted approach in

dealing with one of to-days most pressing health issues!

David J.A. Jenkins

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto;

Clinical Nutrition & Risk Factor Modification Center, St. Michael’s Hospital;

Toronto, Ontario, Canada

Conflict of Interest

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

•  Barilla, Italy – A general food company. Producer of pasta and baked goods. G

•  Solae, St. Louis – The major US producer of soy protein isolate. C,G •  Unilever, Vlaardigen,Netherlands – Major margarine producers

including Becel and Take Control (plant sterol enriched margarine). G, GP

•  Haine Celestial, CA – One of the largest Health Food companies in the US. G

•  Loblaws Supermarkets – Canada’s largest supermarket chain. G, SAB

§  Sanitarium Company, Sydney, Australia – Australia’s largest health food manufacturing company and soy food producer. G, SAB

Conflict of Interest

§  Herbalife International, Century City, CA – A nutraceutical company with an emphasis on sourcing plant derived components for weight loss. SAB

§  Nutritional Fundamentals for Health, Montreal, QE – A new nutraceutical company exploring and aiming to market food derived components for health. SAB

§  Pacific Health Laboratories INC, Matawan, NJ – a nutrition technology company with functional food and nutraceutical products researched and commercialized for sports performance weight loss and type 2 diabetics which can be marketed without prior approval of the FDA. SAB, Stock

§  Metagenics/MetaProteomics, Gig Harbor WA – a company assessing natural products from hops which will positively impact individuals with specific genetic susceptibilities for chronic disease. SAB

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Conflict of Interest

§  Bayer Consumer Care, Springfield NJ – Marketing of nutritional supplements/nutraceuticals. SAB

§  Oldways Preservation Trust, Boston, MA – A not for profit organization promoting traditionally “healthy” ways of eating (eg. Mediterranean Diet, etc.) H

§  Almond Board of California, Modesto, CA – A branch of the USDA (therefore “not for Profit”) to promote the use of almonds. C,H,G

§  The California Strawberry Commission, Watsonville, CA – Another USDA not for profit group to explore possible health benefits and to promote the use of strawberries. SAB

§  Orafti, Tienen, Belgium Development of prebiotics for modification of colonic microflora. SAB, G

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Conflict of Interest

§  Unilever - Canada – Guidelines for the management of hyperlipidemia. G,C,H

§  Agriculture and Agrifoods Canada (AAFC) – SAB §  Canadian Agriculyure Policy Institute (CAPI) – SAB §  White wave- Dean Foods, Colorado – SAB, C, H §  Orafti, Tienen, Belgium Development of prebiotics for modification of

colonic microflora. SAB, G §  Wife and is a Director of Glycemic Index Laboratories, Toronto, CA

– Financial relationship of a spouse §  Kellogg’s, Canada – C, H, SAB §  Quaker Oats, Canada-C, H, SAB

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Conflict of Interest

§  The Coco Cola sugar Advisory Board . C, H,SAB §  Griffin Hospital, New Haven- For the development of the Nuval

System. C, H, SAB §  Abbott Laboratories, Algorithms for Diabetes Management. C, H,

SAB §  The Canola & Flax Councils of Canada. C, H,SAB §  Pulse Canada - SAB §  Saskatchewan Pulse Growers – SAB §  Canadian Institute of Health Research (CIHR) – G §  Canadian Foundation for Innovation (CFI) –G §  Ontario Research Fund (ORF) – G §  Advanced Foods and material Network (AFMNet) – G §  International Tree Nut Council Nutrition Research and

Education Foundation and the Peanut Institute – G, H §  Alpro Soy Foundation - H

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Physiological Effects Low vs. High GI Foods:

Colon Fiber CH2O Sugar etc

↓

0

5

10

15

20

Test Food Groups

Car

bohy

drat

e Lo

sses

(%)

whi

te b

read

othe

rs

oat b

ran

& ba

rley

legu

mes

p<0.001

p<0.01

ns

p<0.001

ns

p<0.001

0

5

10

15

20

0 5 10 15 20 25 30 35

Fiber per 80 g carbohydrate portion (g)

Car

bohy

drat

e lo

sses

(g)

romano beans kidney beans

chick peas

oat bran barley lentils pumpernickel b

bread

pumpernickel a bread

wholemeal bread long grain rice

bulgur rye bread

rice chex corn chex

spaghetti white bread

macaroni instant potato instant rice parboiled rice

0

50

100

150

0 5 10 15 20 25

% Carbohydrate malabsorbed

Gly

cem

ic in

dex,

pub

lishe

d va

lues

rice chex

instant potatocorn chex

wholemeal breadwhite bread

oat branbulgur

rye bread

canned romano beans

canned chick peaslentils

pearl barleycanned kidney beans

Dimpflmeier pumpernickel breadKasseler pumpernickel bread

macaroni

long grain rice

spaghettiparboiled rice

instant rice

Delayed Absorption

Delayed Absorption

↑  Colonic Fermentation

Colon

Small Intestine

Humans: What Gets into the Colon

g/day Fiber (NSP)1 8-18 Starches/Sugars2 5-20% Resistant Starches3 8-40 Inulin 4 1-4 Protein5 3-9 Energy ~5-10%

1 Englyst et al, 1988, 1989; Bingham et al, 1990; 2 Cummings, 1995; 3 Englyst & Cummings, 1987; 4 Roberfroid, 2005; 5 Gibson et al, 1976; Chacko & Cummings, 1988

SCFA

Formate (1-2 mmol/L) Acetate 60 % Systemic Buytrate 20 % Luminal Propionate 20 % Hepatic

Mechanism of SCFA Absorption

Cummings et al, 1995, pg 141.

SCFA/HCO3-

exchange

Diffusion

Fate of SCFA

Acetate

Propionate

Butyrate

Glucose

Colonic Epithelium

Colon

Nitrogen Cycle

↓ N (Urea)

Urea

NH3 + SCFA Urease bacteria

Colon

NH3

↓ N, ↓ pH

↑ Bacterial N + ↑ NH4+

Diet Cells Fiber CH2O

NH4+

Encephalopathy

↑ Bacteria

Feces

Colonic Treatment of Chronic Renal Failure

Week Urea

Arabinogalactan 6 ↓ 11% (15 g bid) Ispaghula (Fibrogel) 8 ↓ 19% (3.5 g bid)

Do the Microflora count? Colonic Microflora and LDL-cholesterol

Jenkins et al., Metabolism. 2005 Jan;54(1):103-12.

Acetate and Lipids (Wolever et al., 1989)

Higher serum cholesterol

(90 mins)

Higher triglyceride

(60 mins)

n=6

TC=5.17 (0.41)

Propionate and Lipids (Wolever et al., 1991)

↓ Total-C

(p=NS)

↓ LDL-C

(p=NS)

↓ TG

(p=NS)

n=6

TC=3.85 (0.56)

Biotransformation of Soy Isoflavones Equol Production: CHO Fermentation

In vitro metabolism of daidzein in a colonic model of fermentation of human fecal flora showing the influence of a high CHO milieu on the rate of conversion of daidzein to the intestinal bacterially derived metabolite equol.

Cassidy, 1991

Hypothesis Equol Production

Daidzein

Equol

Carbohydrate Fermentation

↓ LDL

Colonic Microflora

(Bifidobacteria?)

Soy ± FOS Mean LDL Cholesterol

FOS control soy control FOS & soy

N = 23

* Significantly different from FOS control, P<0.05.

Mean LDL Cholesterol

-10 -8 -6 -4 -2 0 2 4 6

0 2& 4

Weeks

% c

hang

e fr

om b

asel

ine

*

Cancer: Butyrate Paradox

•  ↑ cell proliferation in colonic crypt

•  ↓ proliferation of colon adenocarcinoma cells

Scheppach & Weiler, Curr Opin Clin Nutr Metab Care 2004;7:763-7.

Butyrate:

Colitis: Butyrate Irrigation Study Disease Effect P-value

Harig et al, 1989 DC ↓(5/5) case study

Guellemot et al, 1991 DC ↔ Breuer et al, 1991 UC ↓ ≤ 0.002

Scheppach et al, 1992 UC ↓ <0.01 Breuer et al, 1997 UC ↓ (NS) Steinhart et al, 1996 UC ↔ Cummings, 1997 (review) UC ↔

DC = diversion colitis, UC = ulcerative colitis

Osteoporosis: Rectal Infusion & Ca2+ Absorption

Trinidad TP et al., Am J Clin Nutr 1996;63:574-8.

□ Control (Ca2+ + NaCl)

■ Treatment (Ca2+ & acetate, propionate, or both)

Lactobacillus Therapy for Acute Infectious Diarrhea in Children: A Meta-analysis

Van Niel et al. Pediatrics 2002;109:678-684

C difficile Probiotic (Actimel, Danone) to prevent antibiotics

associated diarrhoea: A randomized double-blind placebo controlled trial (N=134)

Hickson et al. BMJ 2007;335:80

Walkerton. 2000: Animal Husbandry routine antibiotic use for optimal growth = bacterial resistance esp.

E Coli 0157:H7

Antibiotics used in Intensive Animal Husbandry

Lagoons of Fecal effluent from Intensive Animal Husbandry

Summary

•  Alterations in colonic fermentation affects lipid metabolism, biomarkers of colon cancer, immune function and calcium absorption

• Probiotics are effective in the treatment of infectious and antibiotic associated diarrhea