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Dr. David Hermans Sponsored by: European experience with antimicrobial reduction in poultry with MCFA David Hermans Nuscience Group February 25 th 2019 Red Deer | Alberta EU ban on AGP EU ban on AGP US: does not categorize ionophores as medically important antibiotics (FDA, GFI#209, and GFI#152) EU: ionophores are not regulated as antibiotics . Instead, the European Union Regulation (EC) No 1831/2003 categorizes ionophores as “‘coccidiostats’ and histomonostatssubstances intended to kill or inhibit protozoa EU ban on AGP - coccidiostats EU policy > Prudent use of antibiotics (veterinary and human) to avoid development of resistance Use as less antibiotics as possible but as much as is needed to avoid impaired welfare due to illness> Use of ab is monitored on farm level (with action plans when use is too high) > No poultry meat sold with raised without antibiotics’ on label Is this an effective policy?

Dr. David Hermans antimicrobial reduction in

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Page 1: Dr. David Hermans antimicrobial reduction in

Dr. David Hermans

Sponsored by:

European experience withantimicrobial reduction in

poultry with MCFA

David Hermans

Nuscience Group

February 25th 2019

Red Deer | Alberta

EU ban on AGP EU ban on AGP

✓US: does not categorize ionophores as medically important antibiotics (FDA, GFI#209, and GFI#152)

✓ EU: ionophores are not regulated as antibiotics. Instead, the European Union Regulation (EC) No 1831/2003 categorizes ionophores as “‘coccidiostats’ and ‘histomonostats’ substances intended to kill or inhibit protozoa

EU ban on AGP - coccidiostats EU policy

> Prudent use of antibiotics (veterinary and human) to avoid development of resistance

“Use as less antibiotics as possible but as much as is needed to avoidimpaired welfare due to illness”

> Use of ab is monitored on farm level (with action plans when use is too high)

> No poultry meat sold with ‘raised without antibiotics’ on label

Is this an effective policy?

Page 2: Dr. David Hermans antimicrobial reduction in

EU ban on AGP and its impact on antibiotic use on farm level

MARAN report 2017

Reduction in resistance of E. coli in The Netherlands

MARAN report 2017

Management - Attention points

> Example vaccinations:

> More vaccinations against E. coli and Mycoplasma in broiler breeders

> For protection of the day-old chickens and to reduce antibiotic use

Management - Attention points

> Genetics

> Focus on improved egg shell quality, cuticle structure and stronger chick immunity

> Alternative breeds (slow growing, …) - individual sensitivity

> Stocking density (in EU max. 42 kg/m²)

- penalized when too many foodpad dermatitis (welfare issue)

> No reused litter

> Climate (temperature, relative humidity)

> Lighting schedule

Management - Biosecurity

> Scoring Biosecurity:

> Free online application:

Nutritional implications of antibiotic free rearing of broiler chickens

Microbial growth

Bacteria/pathogens

Immune system

Cytokines

Feed intake

Portal flow nutrients

Growth bacteria

Use of nutrients

Fermentation carbohydrates

Transformation bile salts

Absorption fats

Villi length Passage rate

Thickness intestinal wall

Fermentation amino acids

ToxinesAmines

NH3

Endog. losses

GrowthFeed conversion

Faecal-N

Page 3: Dr. David Hermans antimicrobial reduction in

Nutritional implications of antibiotic free rearing of broiler chickens

Advantages

Development immune system

Protection from pathogenic microbes

Providing nutritional compounds (fermentation products)

Stimulation of host defense (mucus)

Disadvantages

Compete with host for nutrients

Potential pathogenic

Deconjugates bile salts

Production of toxic compounds

Stimulation of the immune system has a price (protein)

It is all about a balance between host and microbes!Excess of undigestible protein

➢ Shift in intestinal flora

➢ Fermentation NH3 and biogenic amines intestinal irritation

> Only small effects on broiler performance of AGP in feed with low undigestible crude protein

Protein in feed - digestibility

> Intestinal health affects ideal AA profile

Protein in feed - amino acid balance

> Degradation of bile salts by bacteria

Fats in feed - digestibility

> Effect of infection on fat digestibility

> Broiler feed 7.8% fat

> Broilers infected with Eimeria acervulina at day 18

> Bile salt degradation results in lower fat emulsification

> Fatty acid composition determines digestibility (coconut oil rich in MCFAs)

ADG d18-23 g/d FCR d18-23 Dig. fat d16 % Dig. fat d23 %

Control Animal fat 48.4 1.752 81 87

Inf. Animal fat 36.8 2.054 83 8

Inf. Coconut oil 43.0 1.850 89 49

Inf. Soy oil 38.6 2.037 89 16

Fats in feed - digestibility Additives & feed strategy

> Lot of different products with different MoA available

> Supporting gut health is more than replacing an AGP by an additive

> FLAWS - Feed, Light, Air, Water, Sanitation & Security = good management/biosecurity

Product classes

➢ Phytogenics

➢ Emulsifiers

➢ Exogenous enzymes (NSP, phytate)

➢ Pre- and probiotics

➢Organic acids

➢Medium-chain fatty acids (MCFA)

➢…

Page 4: Dr. David Hermans antimicrobial reduction in

> At start: a broiler chicken has to grow 35 % of their own body weight (+ 1.4 kg growth for a baby of 4 kg)

> Good nutrition at the start is required

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1 6 11 16 21 26 31 36 41

%

chic

ken

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wth

(rela

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bo

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igh

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Days

Chicken growth (relative to own body weight)

Early feeding Early feeding

Hatch window & transportation time

> Delayed access to feed (and water)

> Negative impact on gut health

> Yolk used for maintenance

Early feeding

➢ Access to feed and water directly after a chick hatches

➢ For hatcheries but also on farm level

➢ Yolk used for development

➢ Improved 7 day BW

➢ Less need for antibiotic treatment (E. coli and BCO lameness)

Challenges

> Enterocytes and villi are poorly developed at hatch, and feed deprivation aggravates situation

Broiler villi at 1 day of age with feed and water

Broiler villi at 1 day of age with feed and water restriction

Viola et al, 2003

Maiorka, 2002

Page 5: Dr. David Hermans antimicrobial reduction in

Challenges

> Both gastro-intestinal tract and Bursa are under-developed at hatch:

How are day-old chickens protected against pathogens?

> Innate immunity: day-old chicken can quickly alter cytokine expression (activation of certain

receptors)

> Maternal antibodies (e.g. limited Campylobacter colonization in chickens during the first weeks)

> This indicates the importance of a quick yolk sac resorption and so that the antibodies are

not used as simple energy

> Other solutions: antibacterial additives such as MCFA

Some examples of systems for early feeding

HatchCare by HatchTec Patio by Vencomatic X-Treck by Vencomatic

Additives

> Lot of different products with different MoA available

> Supporting gut health is more than replacing an AGP by an additive

> FLAWS - Feed, Light, Air, Water, Sanitation & Security = good management/biosecurity

Product classes

➢ Phytogenics

➢ Emulsifiers

➢ Exogenous enzymes (NSP, phytate)

➢ Pre- and probiotics

➢Organic acids

➢Medium-chain fatty acids (MCFA)

➢…

What are MCFA?

> Medium Chain Fatty Acids (MCFA) are

> saturated (= no double bonds or ring structures)

> unbranched (= linear molecule)

> monocarboxylic acids (= only 1 carboxylic group -COOH)

> with a chain length of either 6, 8, 10 or 12 carbon atoms

Trivial name Systemic name Structural Formula

Caproic acid Hexanoic acid C6:0

Caprylic acid Octanoic acid C8:0

Capric acid Decanoic acid C10:0

Lauric acid Dodecanoic acid C12:0

MCFA effects - Mode of action

GIT level

Antibacterial

Immunity

Intestinalmorphology

Virulence

MCFA effects - Antibacterial

R-COOH R-COO- + H+

It depends on the pKa

1. MCFA attack the bacteria

> The MCFA is undissociated if the pH of the environment (stomach/GIT) is lower than the

pKa value of the MCFA’s

> In this way the MCFA’s are able to attack the membrane of the bacteria

(which has a negative charge)

Cell membrane = negative charge

Negative charge

Page 6: Dr. David Hermans antimicrobial reduction in

MCFA effects - Antibacterial

2. Degradation of the bacterial cell membrane

> The ‘hydrophylic / lypophylic balance’ (HLB) from MCFA’s is similar like the HLB of the

cell membrane from bacteria

Hydrophylic

Lypophylic

Hydrophylic

Penetration of the MCFA’s in the cell membrane

MCFA’s make a path through the membrane

Intra-cellular

space

Extra-cellular

space

MCFA Cell

content

MCFA effects - Antibacterial

3. MCFA’s dissociate inside the bacterial cell

> Dissociation of the MCFA’s inside the cell

H+

pHMCFAMCFA H+ + MCFA-

MCFA effects - Antibacterial

4. Block the DNA replication

> DNA intercalation → Blocks the DNA replication

H+ + MCFA-

MCFA-

MCFA-

MCFA effects - Antibacterial

Gram Positive

Gram Negative

C6 C8 C10 C12

Esherichia coli Clostridium perfringens

Salmonella Enteritidis

Campylobacter jejuni

MCFA effects - Antibacterial

> In vitro antibacterial activity

End incubation

Start incubation

Page 7: Dr. David Hermans antimicrobial reduction in

MCFA effects - Antibacterial

> In vitro antibacterial activity

Control

+ MCFA

+ Antibiotics

End incubation

Start incubation

MCFA effects - Antibacterial

> MIC values comparison with other acids (in vitro antibacterial activity): Houf, 2005

MIC (g/kg)

Bacterial strain Propionic acid Butyric acid Formic acid Lactic acid MCFA

Aspergillus niger >10 >10 >10 >10 0.5

Bacillus cereus >10 >10 >10 2.5 2.5

Campylobacter jejuni 5 5 5 2.5 0.5

Clostridium perfringens 5 >10 2.5 2.5 0.5

Enterococcus faecalis >10 >10 >10 5 2.5

Enterococcus faecium >10 >10 >10 5 2.5

Escherichia coli >10 >10 >10 5 5

Salmonella Enteritidis >10 >10 >10 5 5

Brachyspira hyodysenteriae >10 >10 >10 >10 2.5

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

Control Formic acid(C1:0)

Acetic acid(C2:0)

Propionic acid(C3:0)

Butyric acid(C4:0)

Caproic acid(C6:0)

Caprylic acid(C8:0)

Capric acid(C10:0)

MCFA effects - Virulence

> Effect of SCFA and MCFA on invasion of Salmonella (Boyen, 2008)

Reduced invasion!

Increased invasion!

MCFA effects - Virulence

> The effect of C6 on Salmonella:

Van Immerseel et al., 2003 (Applied and environmental microbiology))

1,00

2,00

3,00

4,00

5,00

6,00

7,00

8,00

9,00

Control Caproic

log k

ve/g

BEHANDELING

Caeca

liver

spleen

Decreased invasion!

Treatment

MCFA effects - Virulence

> Effect of MCFA on invasion of Salmonella (Evans et al., 2017)

MCFA effects - Intestinal morphology

> Effect of MCFA on the intestinal morphology

> Effect on cell metabolism (MCFA = energy source)

> Reduced microbial load (improved villi structure)

> Morphology of the villi at 42 days - ILVO Belgium

Control MCFA Difference

Duodenum

Villi (µm) 1855 1926

Crypts (µm) 480 304

V/C 4.04a 6.53b + 66 %

Ileum

Villi (µm) 644 752

Crypts (µm) 228 197

V/C 2.94a 3.91b + 33 %

Page 8: Dr. David Hermans antimicrobial reduction in

MCFA effects - Immunity

> Decreased inflammation

> At immunity level

> Less inflammation by accumulation of AGP’s in inflammation cells of the animal

> Energy saving effect

> Similar effects observed for MCFA

> Increased zootechnical performance

Antibacterial

Immunity

Intestinal

morphology

Virulence

Kills the pathogens→ Less infection pressure

Reducing the virulence of pathogens→ Lower activity of pathogens

Improves the intestinal morphology→ Better FCR

Improves the immunity→ Animal immune status of high quality

Prolonged production

cycle0

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Production Chart Commercial Layers

Hen Day production (%) Egg weight (g) Eggmass (g) Avg. Ca Absorption (%) Prolonged cycle

Longer clutches, over a longer period

=> less recovery period

> Increased subject to stress

> impaired health status

> reduced immune status

=> reduced albumen quality

> Reduced Ca-metabolism

> Ca-absorption

> Functioning medullary bone

reduced available Ca

Prolonged production cycle

Increased number of 2nd grade eggs

% haircracks in relation to age (field observations)

Slide 47

Challenge: albumen quality

> Storing of hatching/consumption eggs

> Preventing pathogens reaching the nutrient rich yolk (where they can multiply extensively)

> Effect on hatchability

> Nutritional effect on the embryonic development (also minerals eg Mg,..)

> Antibacterial effect on the protection of the developing embryo

> Effect on day old chick quality (E. coli, Salmonella, ...) and its growth

Slide 48

Page 9: Dr. David Hermans antimicrobial reduction in

Slide 49

Challenge: albumen quality Challenge: hatchability

Slide 50

Source: Decuypere et al.

BM = before moulting

AM = after moulting

> MCFA improves the calcium absorption (Sayago et al.,

2008)

> Energy for the enterocytes (important for the active

calcium transport

> Higher absorption capacity (important for the passive

calcium transport)

> Increased availability of nutrients (proteins for in the

albumen, vitamins, organic material) for egg production

and eggshell formation

Slide 51

MCFA: effects

> Because of its effect on gut health reducing the need of

proteins for activation of the immune system and improving

gut integrity MCFA results in:

> a positive effect of HD production

> a significant decrease of haircracks

> a positive effect on hatch of fertiles and DOC quality

> a positive effect on early broiler performance

MCFA: effects

Closing remarks

“No 100% solution for ABF but MCFA can - together with the choices we make in proper management and when formulating and producing our

diets - certainly contribute to a reduction in the use of antibiotics”European experience withantimicrobial reduction in

poultry with MCFA

David Hermans

Nuscience Group

February 25th 2019

Red Deer | Alberta

Thank you for yourkind attention!