03. Hani El-Nezami - Probiotics Mycotoxins

7232019 03 Hani El-Nezami - Probiotics Mycotoxins

httpslidepdfcomreaderfull03-hani-el-nezami-probiotics-mycotoxins 130

Interaction of Probiotics andMycotoxins ndash Benefits to Human

Health

-

School of Biological Sciences

University of Hong Kong

ILSI SEA Region 6th Asian Conference on Food and Nutrition Safety (Nov 2012)httpwwwilsiorgSEA_RegionPagesViewEventDetailsaspxWebId=4D540914-EEB6-40E4-89EB-0B73BA3D76C1ampListId=478BE3CB-581B-4BA2-A280-

8E00CCB26F9CampItemID=66



Probioticsbull Definition

Living microorganisms when administered in adequateamounts confer health benefits on the host

Dr Minoni ShirotaFirst developed L casei Sirotaas a commercial product in 1935



983120983154983151983138983145983151983156983145983139983155 991251 983108983137983145983148983161 983141983160983137983149983152983148983141

983107983144983141983141983155983141

1 Fermented Milk Products

983116983137983155983155983145

983110983154983151983162983141983150 983161983151983143983157983154983156 983113983139983141 983139983154983141983137983149

983123983149983151983151983156983144983145983141983117983145983148983147

983126983137983148983145983151 983111983141983142983145983148983157983155983214 9830900 983161983141983137983154983155 983151983142 983152983154983151983138983145983151983156983145983139 983140983137983145983154983161 983152983154983151983140983157983139983156983155 983145983150 983109983157983154983151983152983141



Probiotics ndash Daily example

2 Food amp Drinks 3 Pharmaceutical products

983117983145983150983156 983139983137983150983140983145983141983155

983107983141983154983141983137983148 983113983150983142983137983150983156 983142983151983154983149983157983148983137

983107983137983150983140983161 amp 983143983154983137983150983151983148983137 983138983137983154983155

983107983151983151983147983145983141983155

983120983154983151983138983145983151983156983145983139983155 983155983157983152983152983148983141983149983141983150983156In form ofTablets Capsules GranulesSingle or Cocktail of species

983109983150983139983137983152983155983157983148983137983156983145983151983150 983144983141983148983152 983152983154983151983156983141983139983156 983152983154983151983138983145983151983156983145983139983155 983142983154983151983149983098

983085983105983145983154 amp 983149983151983145983155983156983157983154983141 (983141983155983152 983137983150983137983141983154983151983138983145983139 983155983152983141983139983145983141983155)983085983123983156983151983149983137983139983144 983137983139983145983140

Dosage109 ndash 1010 bacteria day adult



Probiotics have several mechanisms of

action that may contribute to human health

983112983151983159 983137983138983151983157983156 983145983150983156983141983154983137983139983156983145983151983150983155 983159983145983156983144 983142983151983151983140 983156983151983160983145983150983155983103983103983103983103



Hepatocellular Carcinoma

(HCC)bull Hepatocellular carcinoma

(HCC) ranks as the fifthmost common cancer in

the world with anestimating 473000 newcases annuallyaccounting for 54 ofall human cancer cases

bull Late presentationtypically males aged 66with chronic liverdisease

bull Median survival of 6months from time ofdiagnosis

bull Surgery is the onlypotentially curable formof treatment



Risk factors for HCC

bull Viral

Chronic hepatitis B

Chronic hepatitis C

bull Preexisting liver disease

-Metabolic liver disease

-Alcohol abuse

Adenomabull Environmental

Aflatoxin

Contraceptives and androgens



The aflatoxins

bull Turkey ldquoXrdquo Disease

ndash Fungal infection byAspergillus flavus and

ndash Primary contamination

bull High energy contentfoods eg grain nutand soy products

ndash Secondary contamination

bull Dairy products meatamp eggs



Commodities in which aflatoxins

have been detected

Flour Cocoa

Corn meal CheesePeanut Sausage

Meat pies Bread

Milk Macaroni

Cottonseed CopraCassava Cooked meat

Brazil nuts Pistachio nuts

Oilseeds Rice

Pumpkin seeds Soy



TOXIC EFFECTS OF AFLATOXINTOXIC EFFECTS OF AFLATOXIN

bull Human

ndash Aflatoxin B1 is highly mutagenic probablythrough mechanisms of epoxidation resultingin covalent binding to DNA

ndash A specific mutation at the third base ofcodon 249 of the tumor-suppressor gene p53has been described in HCC tissue and

significantly associated with exposure toaflatoxin B1





Populations at risk of aflatoxin exposure

Williams et al Am J Clin Nutr 801106-1122 2004



Chronic hepatitis B together with exposure

to dietary aflatoxins increases the riskof liver cancer

59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e

o f o f p r i m a r y l i

p r i m a r y l i

HBVHBV(HBsAg)

AflatoxinsAflatoxins(urinary

biomarkers)

HBV andaflatoxinsHBV andaflatoxins

Adapted from Qian et al 1994

No riskNo riskfactorsfactors



Available options for solving the

problem

Once food is contaminated with toxins there are only two options

if the food is to be used

ndash the toxin can be removed

ndash the toxin can be degraded into less toxic or non-toxic

compounds



Control measures

bullPhysical control (eg UV radiation electronic sorting)

983085 suitable for very limited products

bullChemical control (eg ammoniation)

- health effects are not fully studied

bullMonitoring AF levels and rejection of produce

983085 extremely costly option



Aflatoxins in food

Duodenum

IleumLiver

Absorption (portal circulation)

Systemiccirculation

Blood

O

OO OCH3

O O

AFB1

Strategies for intervention at

individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver

Blockingreducing absorption of AFB1 from

the small intestine

Aflatoxin + blocker

Small

intestine

Unabsorbedaflatoxins

Systemiccirculation




Requirements for dietary tools of blockingreducing aflatoxin absorption in humans

bull Part of normal human diet

bull Long history of safe use

bull Ab e to bind a ran e o har u co ounds inc udin

aflatoxins

bull Binding takes place immediately and is stable underGIT conditions

bull No effect on absorption of micro and macronutrients

bull Inexpensive and practical for food enrichments



Lactic acid bacteria(LAB)

bull LAB involved in the production of fermented foods

o one quarter of our diet

o characterised by safe history

o extended shelf life com ared to raw materials

bull LAB has some health effects

o growth inhibition of food spoiling bacteria

o production of antimicrobial compounds

o probiotic effects as live organisms in food



Kinetic studies on binding

and release of toxins(dose-response)



In vitro binding assays with AF

Mechanisms of binding

(chemical and structural factors)



In vitro toxicity studies(to examine if the bindingwill detoxicate the AFs)


Selection of bacteria with GRAS status(available commercially or isolated from microflora of

healthy humans)

Selection of bacteria with good binding propertiesof AFs and ability to deactivate AFs

In vivo bindingof AF

Clinical trials in populations exposed to AFs(body burden and biomarkers)

Ex vivo ligated loop in chicksEx vivo ligated loop in chicks Feeding studiesin animals

Feeding studiesin animals

Stability of complex

effect on absorption and bioavailability



bull Certain strains oflactobacilli are capableof binding up to 80 ofAFB1 in vitro (El-Nezami

et al 1996 1998abc)Fusarium toxins (El-Nezami et al 2002ab2004) PhIP and Trp-P-1(Haskard et al 2001)

Aflatoxin is bound by probiotic bacteria ndash invitro evidence

60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli

bullAFB1 is predominantlybound to a carbohydratemoiety on the surface ofthe bacteria (Haskard etal 2002)

bull The complex formed

between the bacteria andAFB1 is stable underdifferent conditions(Haskard et al 2002 Leeet al 2003)

0 4 24 48 720

20

40

A F

B 1 r e m o v e d f r

Period of incubation

El-Nezami et al Food Chem Toxicol 1998



Ex vivo study in chicks

The concentration of AFB1 plusmnplusmnplusmnplusmn SD extracted from

Group Duodenal tissueb Soluble fractionc Insoluble fraction of

El-Nezami et al (2000) ) Journal of Food Protection

JGratz S et al (2005) Journal of FoodProtection

of luminal fluid

luminal fluid

1min 60 min 1 min 60 min 1 min 60 min

AFB1 only 027 plusmnplusmnplusmnplusmn 009 ND 104 plusmnplusmnplusmnplusmn 036 005plusmnplusmnplusmnplusmn001 ND ND

LBGG+AFB1 007 plusmnplusmnplusmnplusmn 005 ND 048 plusmnplusmnplusmnplusmn 015 ND 076plusmnplusmnplusmnplusmn004 138plusmnplusmnplusmnplusmn016

LC705+AFB1 017 plusmnplusmnplusmnplusmn 011 ND 058 plusmnplusmnplusmnplusmn 010 008 plusmnplusmnplusmnplusmn 006 054plusmnplusmnplusmnplusmn010 107plusmnplusmnplusmnplusmn012

PJS+AFB1 010 plusmnplusmnplusmnplusmn 005 ND 067 plusmnplusmnplusmnplusmn 013 013 plusmnplusmnplusmnplusmn 002 055plusmnplusmnplusmnplusmn011 124plusmnplusmnplusmnplusmn006



0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m

s e c x 1 0 e - 6 ) Transport of AFB1

Intestinal AFB1 transport and toxicity

Caco-2 cells

Semi-permeable filter

Bacteria

apical

basolateral

Gratz S et al (2007) Applied and Environmental Microbiology

bull Transport of AFB1 through monolayer was reduced by GG

bull AFB1 induced TER (membrane integrity) reduction wasattenuated

bull

AFB1 induced DNA damage was attenuated



3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

plusmn GGplusmn GGplusmn GGplusmn GGplusmn GGplusmn GG

In vivo protective effects of probiotics against

AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight

AFB1 (15 mgkg bw single dose on day 0)

GG (5x1010CFU daily for 6 days)

Body weightBody weight



Rat results

GG administration

bull Increased fecal AFB1 by 122bull Increased fecal AFM1 by 152

bull Decreased plasma AFB1-albumin by 29

bull Prevented body weight loss




WHY CHINAbull Primary liver cancer (PLC) is one of the most common cancers in

China

bull There more than 250000 new cases diagnosed yearly with livercancer in China

bull The mortality rates both in rural and urban areas are 25 and 21per 100 000 respectively in the EU 3 per 100000

bull The ain 3 actors or the de elo ent o li er cancer are

prevalent in China Aflatoxins are consistent contaminants of thefood supply in China HBV and HCV are endemics in China

bull 500000000 individual infected with HBV(250000000 in China)

bull 170000000 individuals infected with HCV(10000000 in China)

bull 1000000 individuals dies annually because of complicationassociated with HBV similar figure also expected for HCV

(250000 in China)



Intervention andsampling

Follow-up andaflatoxin

measurementRecruitment

300 healthy Chinese men

screened for urinary AFM1

142 subjects haddetectable level of AFM1

in their urine

The subjects were rando-

mized in two groups re-ceiving either 2 placeboor 2 probiotic capsulesdfor 5 weeksBioprofitreg containing 1010

Follow-up sample at day70 (5 weeks after dis-continuation of thetreatments)

Fecal and urinary

Probiotic intervention in China

90 recruited based onphysicianrsquos examinationand blood chemistry

c u capsu e

Fecal urine and bloodsamples were collected atbaseline (day 1) and duringintervention (days 21 and35) Additional fecal

samples were collected atdays 235

aflatoxin M1 and Q1

concentrations weremeasured by HPLC AFB-

N7-guanine was used as avalidated biomarker forreduction in HCC

2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70



Metabolic transformation of

aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo

Probiotic supplementation reduces the urinaryexcretion of AFB1ndashN7-guanine a biomarker of

biologically effective dose of exposure to AFB1

Baseline W eek 3 W eek 5 Fo llow-up U r i n a r y

A F B 1 - N 7 - g

u

01

0 2

03

04

El-Nezami et al Am J Clin Nutr 2006



What our findings mean

Egner et al Mutation Res 523-524209-216 2003



Probioticsbull Definition

Living microorganisms when administered in adequateamounts confer health benefits on the host

Dr Minoni ShirotaFirst developed L casei Sirotaas a commercial product in 1935



983120983154983151983138983145983151983156983145983139983155 991251 983108983137983145983148983161 983141983160983137983149983152983148983141

983107983144983141983141983155983141


983116983137983155983155983145

983110983154983151983162983141983150 983161983151983143983157983154983156 983113983139983141 983139983154983141983137983149

983123983149983151983151983156983144983145983141983117983145983148983147

983126983137983148983145983151 983111983141983142983145983148983157983155983214 9830900 983161983141983137983154983155 983151983142 983152983154983151983138983145983151983156983145983139 983140983137983145983154983161 983152983154983151983140983157983139983156983155 983145983150 983109983157983154983151983152983141





983117983145983150983156 983139983137983150983140983145983141983155

983107983141983154983141983137983148 983113983150983142983137983150983156 983142983151983154983149983157983148983137

983107983137983150983140983161 amp 983143983154983137983150983151983148983137 983138983137983154983155

983107983151983151983147983145983141983155


983109983150983139983137983152983155983157983148983137983156983145983151983150 983144983141983148983152 983152983154983151983156983141983139983156 983152983154983151983138983145983151983156983145983139983155 983142983154983151983149983098

983085983105983145983154 amp 983149983151983145983155983156983157983154983141 (983141983155983152 983137983150983137983141983154983151983138983145983139 983155983152983141983139983145983141983155)983085983123983156983151983149983137983139983144 983137983139983145983140






983112983151983159 983137983138983151983157983156 983145983150983156983141983154983137983139983156983145983151983150983155 983159983145983156983144 983142983151983151983140 983156983151983160983145983150983155983103983103983103983103













bull Viral

Chronic hepatitis B

Chronic hepatitis C



-Alcohol abuse


Aflatoxin




The aflatoxins










have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








983120983154983151983138983145983151983156983145983139983155 991251 983108983137983145983148983161 983141983160983137983149983152983148983141

983107983144983141983141983155983141


983116983137983155983155983145

983110983154983151983162983141983150 983161983151983143983157983154983156 983113983139983141 983139983154983141983137983149

983123983149983151983151983156983144983145983141983117983145983148983147

983126983137983148983145983151 983111983141983142983145983148983157983155983214 9830900 983161983141983137983154983155 983151983142 983152983154983151983138983145983151983156983145983139 983140983137983145983154983161 983152983154983151983140983157983139983156983155 983145983150 983109983157983154983151983152983141





983117983145983150983156 983139983137983150983140983145983141983155

983107983141983154983141983137983148 983113983150983142983137983150983156 983142983151983154983149983157983148983137

983107983137983150983140983161 amp 983143983154983137983150983151983148983137 983138983137983154983155

983107983151983151983147983145983141983155


983109983150983139983137983152983155983157983148983137983156983145983151983150 983144983141983148983152 983152983154983151983156983141983139983156 983152983154983151983138983145983151983156983145983139983155 983142983154983151983149983098

983085983105983145983154 amp 983149983151983145983155983156983157983154983141 (983141983155983152 983137983150983137983141983154983151983138983145983139 983155983152983141983139983145983141983155)983085983123983156983151983149983137983139983144 983137983139983145983140






983112983151983159 983137983138983151983157983156 983145983150983156983141983154983137983139983156983145983151983150983155 983159983145983156983144 983142983151983151983140 983156983151983160983145983150983155983103983103983103983103













bull Viral

Chronic hepatitis B

Chronic hepatitis C



-Alcohol abuse


Aflatoxin




The aflatoxins










have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04










983117983145983150983156 983139983137983150983140983145983141983155

983107983141983154983141983137983148 983113983150983142983137983150983156 983142983151983154983149983157983148983137

983107983137983150983140983161 amp 983143983154983137983150983151983148983137 983138983137983154983155

983107983151983151983147983145983141983155


983109983150983139983137983152983155983157983148983137983156983145983151983150 983144983141983148983152 983152983154983151983156983141983139983156 983152983154983151983138983145983151983156983145983139983155 983142983154983151983149983098

983085983105983145983154 amp 983149983151983145983155983156983157983154983141 (983141983155983152 983137983150983137983141983154983151983138983145983139 983155983152983141983139983145983141983155)983085983123983156983151983149983137983139983144 983137983139983145983140






983112983151983159 983137983138983151983157983156 983145983150983156983141983154983137983139983156983145983151983150983155 983159983145983156983144 983142983151983151983140 983156983151983160983145983150983155983103983103983103983103













bull Viral

Chronic hepatitis B

Chronic hepatitis C



-Alcohol abuse


Aflatoxin




The aflatoxins










have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04










983112983151983159 983137983138983151983157983156 983145983150983156983141983154983137983139983156983145983151983150983155 983159983145983156983144 983142983151983151983140 983156983151983160983145983150983155983103983103983103983103













bull Viral

Chronic hepatitis B

Chronic hepatitis C



-Alcohol abuse


Aflatoxin




The aflatoxins










have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04


















bull Viral

Chronic hepatitis B

Chronic hepatitis C



-Alcohol abuse


Aflatoxin




The aflatoxins










have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








The aflatoxins










have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04









have been detected

Flour Cocoa


Meat pies Bread

Milk Macaroni



Oilseeds Rice

Pumpkin seeds Soy




bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04









bull Human














59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04
















59460

R i s k

R i s k

e r c a n c e r

e r c a n c e r

7334

1

0

20 R e l a t i v

e

R e l a t i v

e


p r i m a r y l i

HBVHBV(HBsAg)


biomarkers)







problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04









problem





compounds



Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








Control measures









Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








Aflatoxins in food

Duodenum

IleumLiver


Systemiccirculation

Blood

O

OO OCH3

O O

AFB1


individual level

Jejunum

Feces (unabsorbed)

UrineBreast milk

ColonMetabolism

Toxicproducts

Non toxicproducts



Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








Aflatoxin

Portal vein

Liver


the small intestine

Aflatoxin + blocker

Small

intestine


Systemiccirculation








aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04












aflatoxins





























healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04































healthy humans)













60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04











60

80

100

m

s o l u t i o n

LGG

LC705

acido

gasseri

ShirotaPJS

E coli




0 4 24 48 720

20

40

A F











of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04













of luminal fluid

luminal fluid








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








0

5

10

15

20

25

30

35

no GG 5 GG

GG (1010

CFUmL)

P e ( c m



Caco-2 cells


Bacteria

apical

basolateral




bull




3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








3210-1-23days

AFB1

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine

Feces

Urine



AFB1 toxicity

Feces

Urine

Blood (ALT)

Body weight






Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








Rat results

GG administration








China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04









China








(250000 in China)









in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04














in their urine




Fecal and urinary



c u capsu e



aflatoxin M1 and Q1



2Study days

(Follow-up)

35

(Baseline)

21531

(Probioticplacebo)

70




aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04









aflatoxin B1



n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04








n i n e ( n g m l )

06

07Probiotic

Placebo




A F B 1 - N 7 - g

u

01

0 2

03

04






03. Hani El-Nezami - Probiotics Mycotoxins

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Transcript of 03. Hani El-Nezami - Probiotics Mycotoxins