QUAND LA NUTRITION PEUT ACTIONNER UN LEVIER … D Bravo Session AFTAA.pdf · BESOINS DES ANIMAUX...

7 Décembre 2016

QUAND LA NUTRITION PEUT ACTIONNER UN LEVIER IMMUNITAIRE

David M. Bravo (PhD) Chief Innovation Officer

PRÉAMBULE

AFTAA

NUTRIMENTS

ANTI NUTRIMENTS

AVANT 1990

1990

INTESTIN DIGÈRE & ABSORBE

INTESTIN VULNERABLE

VISCOSITÉ, TOXINES

BESOINS DES ANIMAUX

DISPONIBILITÉ NUTRIMENTS

PROGRAMME NUTRITIONNELS

STRATÉGIES ANTI-TOXINES

ENZYMES

PRODUCTION ZOOTECHNIQUE

Influence ALIMENT

PRÉAMBULE

AFTAA

PRODUCTION ZOOTECHNIQUE

BONNE

MAUVAISE

QUALITE NUTRITION ALIMENT

BONNE MAUVAISE

PRÉAMBULE

AFTAA

« SANTÉ DIGESTIVE»

PRÉAMBULE

AFTAA

NON-NUTRIMENTS

• L’intestin est un organe sensoriel intelligent.

• Par des voies non-nutritionnelles, le nutritionniste peut communiquer avec l’intestin.

• Cela provoque des réactions physiologiques (immunité, inflammation, sécrétions hormonales).

• Ce qui améliore la performance zootechnique, la santé et le bien être des animaux d’élevage.

OBJECTIF DE LA PRÉSENTATION

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• L’intestin, un organe sensoriel intelligent

• Exemple pratique # 1

• Exemple pratique # 2

• Messages à ramener à la maison

PLAN

L’INTESTIN, UN ORGANE SENSORIEL

INTELLIGENT

• Un organe sensoriel intelligent:

• Détecte une information [sensoriel]

• Transmet à un système opérateur [sensoriel]

• Analyse l’information [intelligent]

• Réagit ou provoque une réaction [intelligent]

?

L'INTESTIN UN ORGANE SENSORIEL INTELLIGENT

AFTAA

Furn

ess

& B

ravo

(u

np

ub

lish

ed)

L'INTESTIN UN ORGANE SENSORIEL INTELLIGENT

AFTAA

CELLULE ENTERO

ENDOCRINE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

Source: Silbering & Benton (2010, Embo Reports)

DÉTECTION

TRADUCTION

ALIMENT

K CELLS

L CELLS

D CELLS G CELLS

N CELLS

EC CELLS

A CELLS

GIP

PYY

SST GASTRIN

NTS

5HT

GHRELIN

Source: Furness & Bravo (unpublished)

WEANING PIGLET DUODENUM DOBLE LABELING PGP95 AND VIP

Source: Shirazi-Beechey & Bravo (unpublished)

CELLULE ENTERO

ENDOCRINE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ENTEROCYTE

ANALYSE COMMUNICATION AVEC LE CERVEAU

REACTION ORGANE DISTAL

REACTION LOCALE

INTESTIN ORGANE SENSORIEL

INTELLIGENT

ALIMENT PAS QUE NUTRITION

DIET =

INFORMATION

AMELIORATION PRODUCTION

SANTÉ BIEN ÊTRE ANIMAUX

DÉTECTION

TRADUCTION

ALIMENT

13

plicae circulares

WEANING PIGLET DUODENUM (x4) TLR4 (green) / ChA (red) / Dapi (blue)

Source: Shirazi-Beechey & Bravo (unpublished)

L'INTESTIN UN ORGANE SENSORIEL INTELLIGENT

AFTAA

Furn

ess

& B

ravo

(u

np

ub

lish

ed)

CHICKEN DENDRITIC CELLS LABELING PTSO

Source: Lillehoj & Bravo (unpublished)

Source: adapted from Gill, Wlordarska & Finlay (2010, Nature Immunology)

L'INTESTIN UN ORGANE SENSORIEL INTELLIGENT

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MICROBIAL ECOSYSTEM

NON NUTRIENTS DIET

ENDOCRINE CELLS

DENDRITIC CELLS

BLOOD STREAM

ENTERIC NEURONS

IMMUNE FUNCTION

LOCAL RESPONSE

GLOBAL RESPONSE

REACTION OF THE ANIMAL

TO ITS DIET

FEED INTAKE; GUT TRANSIT TIME DIGESTIVE SECRETION,

CARBOHYDRATE HOMEOSTATIS HEALTH

MOLECULE NON NUTRITIONNELLE

RECEPTEUR REPONSE

PHYSIOLOGIQUE

REPONSE ZOOTECHNIQUE

ADDITIF

L'INTESTIN UN ORGANE SENSORIEL INTELLIGENT

AFTAA

CAS PRATIQUE #1

EDULCORANT INTENSE

T1R2/3 Ć ENTEROENDOCRINE

SECRETION GLP2

EFF. ALIMENTAIRE SEVRAGE

ADDITIF

GLP-2

Gut vasodilation

Cell survival

Mucosa growth

Hexose absorption

Motility

Gastric emptying

Gastric secretion

Inflammation EEC L CELL

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

GLP-2 prevents tissue damage from parasitic infection

*** = P < 0.001; Connor et al., 2013 J. Dairy Sci.

Nit

ro

tyro

sin

e s

tain

ing

(pix

els

/ce

ll,

ce

cu

m)

C o n tr o l G L P -2 C o n tr o l G L P -2

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

U n in f e c t e dIn f e c t e d

( E im e r ia b o v is )

* * *

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

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ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

T1R2 T1R3

T1R2 T1R3

TONGUE

SWEET VERY

INTAKE

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α-gust GLP-2 Merged

TIR3 GLP-2 Merged

TIR2 GLP-2 Merged

Source: Moran , Al-Rammahi, Arora, Batchelor, Coulter, Ionescu, Bravo and Shirazi-beechey (2010, Br. J. Nutr.)

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

ChA T1R3 Merged

Gust ChA Merged

T1R2 ChA Merged

SOURCE: MORAN , AL-RAMMAHI, BRAVO, CALSAMIGLIA & SHIRAZI-BEECHEY (2014, J. DAIRY SCI.)

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

T1R2 GLP-2 Merged

SOURCE: MORAN , AL-RAMMAHI, BRAVO, CALSAMIGLIA & SHIRAZI-BEECHEY (2014, J. DAIRY SCI.)

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

α-gust GLP-2 Merged

TIR3 GLP-2 Merged

TIR2 GLP-2 Merged

Source: Moran , Al-Rammahi, Arora, Batchelor, Coulter, Ionescu, Bravo and Shirazi-beechey (2010, Br. J. Nutr.)

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

GLP-2

T1R2

Source: Bravo & Shirazi-Beechey (unpublished data)

T1R2 T1R3

ENTEROCYTE

ENTEROENDOCRINE

GLP-2

S

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

27

DIGESTIVE LUMEN

GUT MUCOSA

ENTERIC NEURONS

ENTEROENDOCRINE CELL

ENTEROCYTES

INTERNAL COMPARTMENT

T1R2

T1R3

ENTEROCYTE

ENTEROCYTE

ENTEROENDOCRINE

GUSDUCINE ®

GLP-2 GLP-2 GLP-2

RECEPTOR

ENTERIC NEURON

- + - + -

+ - +

- + -

+ - +

- + - +

- + -

EDUL

29

DIGESTIVE LUMEN

GUT MUCOSA

ENTERIC NEURONS

ENTEROENDOCRINE CELL

ENTEROCYTES

INTERNAL COMPARTMENT

NEURO TRANSMITER

ENTERIC NEURONS

SGLT1

STEM CELLS

✖ ✖ ✖

+ - + - + -

+ - + - + - +

+ +

- -

- -

- - -

+ +

+ + +

+ -

+ - -

EDUL releases of GLP-2 from ruminant intestine

GL

P-2

se

cre

tio

n

(% o

f c

on

tro

l)

C o n tr o l S u c r a m

0

5 0

1 0 0

1 5 0

2 0 0* * *

Moran et al., 2014. J. Dairy Sci.

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

EDUL

Source: Moran , Al-Rammahi, Bravo, Calsamiglia & Shirazi-Beechey (2014, J. Dairy Sci.)

Cal

f

Cal

f + S

uc

Wea

ned

Wea

ned +

Suc

0

50

100

150

200

250

D-g

luc

os

e u

pta

ke

(pm

ol s

-1 (

mg

pro

tein

)-1) ***

***

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

AFTAA

0

5

10

15

20

25

30

CON INF GLP2 SUC

DSI

P < 0.02

A

B B

*

A

0

5,000

10,000

15,000

20,000

25,000

30,000

INF GLP2 SUC

Oo

cyst

s/g

fece

s

*** P < 0.002

B

Source: Connor, Wall, Bravo, Evock-Clover, Elsasser, Baldwin, Santín-Duran, Kahl, Vinyard & Walker (2016, J. Dairy Sci.)

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

EDUL

EDUL

AFTAA

Av

era

ge

Da

ily

Ga

in

(lb

/d

ay

)

C o n tro l C o n tro l G LP - 2 S u c ra m

0 .0

0 .2

0 .4

0 .6

U n in f e c t e dIn f e c t e d

(C r y p to s p o r id iu m )

Connor, Wall, Bravo; New unpublished data

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #1

EDUL

AFTAA

NON NUTRIMENT

INTESTIN ORGANE SENSORIEL

[SYSTÈME NEURO ENDOCRINIEN]

AMÉLIORATION PERFORMANCE, SANTÉ , BIEN-ÊTRE

ANIMAUX ÉLEVAGE

SYSTÈME IMMUNITAIRE EXEMPLE

AFTAA

CAPSAICIN

TRPV1 Ć DENDRITIQUE

ANTI INFLAMATOIRE

EFF. ALIMENTAIRE PROTECTION DIGESTIVE

ADDITIF

CAS PRATIQUE #2

MECHANICAL DEFENSES (THORNS, HARD SHELL)

PHYSICAL STRUCTURES (THICK SKIN, FUR)

DETOXIFICATION PHASE I (MODIFICATION, EG. CYP450S)

BEHAVIORAL STRATEGIES (AVOIDANCE, LIMIT INTAKE)

CONCENTRATION IN VULNERABLE PARTS (FRUITS, SPROUTS)

CHEMICAL DEFENSES (NOXIOUS CHEMICALS)

SECONDARY TOXICITY

DETOXIFICATION PHASE II (CONJUGATION: GSH, SULFATE, GLUCURONIC ACID)

DETOXIFICATION PHASE III (EXCRETION: MULTIDRUG RESISTANCE PROTEINS)

DIVERSIFICATION OF CHEMICALS

REC

IPR

OC

AL

EVO

LUTI

ON

ANIMAL KINGDOM PLANT KINGDOM

ANIMAL KINGDOM PLANT KINGDOM

CAPSAICIN

CINNAM- ALDEHYDE

FERUTININE

TRPV1

TRPA1

ER

REP

ON

SE P

HY

SIO

LOG

IQU

E D

’IN

TER

ET Z

OO

TEC

HN

IQU

E

<

ANIMAL KINGDOM

PLANT KINGDOM

Source: (1): Furness & Bravo (unpublished data) (2) Wenning, Neblung, Strauß, Wolfs, Sappok, Hoth, Schwarz (2011, Bioch. Biophys. Act.) (3): Fernandes, Liang, Smillie, Kaiser, Purcell, Rivett, Alam, Howat, Collins, Thompson, Keeble, Riffo-Vasquez, Bruce and Brain (2012, J. Immunol.)

• TRPV1 • Agonist: capsaicin • not in gut epithelial cells (1) • present in dendritic cells (2) • controls inflammation (3)

CAPSAICIN

TRPV1

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #2

AFTAA

Source: Liu, Song, Che, Almeida, Lee, Bravo, Maddox & Pettigrew (2013, J. Anim. Sci.)

0

5

10

15

20

25

30

35

40

45

d0-11 d0-11

Sham E. coli CON

CAP

GAR

TUR

Sham vs. E. coli: P < 0.05

CON vs. PE P < 0.05

CON vs. PE P < 0.05

* * *

*

* *

FREQUENCY OF DIARRHEA (%)

CAP = 10 ppm capsicum oleor. GAR = 10 ppm garlic metabolite TUR = 10 ppm turmeric oleor.

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #2

AFTAA

Source: Liu, Che, Song, Almeida, Lee, Bravo, Van Alstine & Pettigrew (2013, J. Anim. Sci.)

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #2

AFTAA

Source: Liu, Che, Song, Almeida, Lee, Bravo, Van Alstine & Pettigrew (2013, J. Anim. Sci.)

AFTAA

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #2

NON NUTRIMENT

INTESTIN ORGANE SENSORIEL

[SYSTÈME IMMUNITAIRE]

AMÉLIORATION PERFORMANCE, SANTÉ , BIEN-ÊTRE

ANIMAUX ÉLEVAGE

AFTAA

ORGAN SENSORIEL INTELLIGENT CAS PRATIQUE #2

MESSAGES À RAMENER À LA MAISON !

MESSAGES POUR LA MAISON !

• L’INTESTIN, UN ORGANE CARDINAL.

• UN ORGANE SENSORIEL INTELLIGENT.

• MOLECULES / RECEPTEUR.

• PHYSIOLOGIE ZOOTECHNIE.

• NOUVEAU PARADIGME: NON-NUTRITION.