Alternative products to enhance intestinal health.

Experiences in EU.
Dr.Hilde Van Meirhaeghe - Vetworks
RSA – AFMA 2013

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Overview
 Introduction

 Importance of gut health and contributing factors

 Alternative solutions to improve gut health

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Introduction
 Challenges poultry production:
 Provide animal protein for the growing world population in a sustainable
way
 Guarantee food safety
 Respect the environment – waste management
 Keep it profitable

 EU policy: meat production safe ‘from stable to table’

 EFSA : concerns of Antimicrobial Resistance AMR in humans
 2006 Antimicrobial Growth Promotors AGP banned
 Reduction antimicrobial use in animal

 Non EU countries: KFC and McDonald’s announced to

promote AGP-free poultry meats

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Public opinion AMR
 Dame Sally Davies, Chief Medical Officer for England,
warns that within the next 20 years, people having simple
operations may die because there will be no antibiotics
left that can deal effectively with routine infections.

 The danger posed by growing resistance to antibiotics

should be ranked along with terrorism on a list of threats
to the nation.

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Facts – emotions - policies

MRSA

ESBL

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Link AMR humans –animals?
 Looks simple but…..

 What will be the impact of reduction of antibiotic use in

food animals?
 Very difficult to measure…but EU ‘precautionary principle’
 ‘One World – One Health’.

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Epidemiology of AMR is very complex

adapted and modified from Linton [1977] by Rebecca Irwin, Health Canada[Prescott 2000] and IFT.
Good news: AMR can be reversed

Dutil et al. 2010

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Introduction

 EU regulations food animal production controversy

- Since the ban of AGP more therapeutic AB use
- Reduction of antimicrobial resistance by reducing antibiotic
use in food animals
• The Netherlands: 50% reduction ( imposed by the goverment)
• Germany: voluntary reduction in some integrations ( imposed
by retailers)
• Belgium: ‘prudent use of AM’ – formularium, monitoring AB use

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EU: Antibiotic use in poultry
 AB use mainly in broilers (not in layers, eggs for consumption)

 70% of the antibiotic use in is for problems related to gut

health

 To reduce antibiotic use: improve intestinal health

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Overview
 Introduction

 Importance of gut health and contributing factors

 Alternative solutions to improve gut health

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Intestinal health and integrity
Efficiency of ingredient digestion and nutrient absorption
depends on

 Structural integrity and physiologic activity of the gut

 Balance between microbial ecosystem and the host defence

mechanisms

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Intestinal health and integrity
 Structural integrity
• Long and wide villi: greater surface for absorption
• Small crypts: lower tissue turn over, less energy and protein
required for recovery
• Goblet cells: produce protective mucines
• Strong tight junctions:
• prevent bacteria and toxic substances to enter the cells and the
blood, and cause inflammation and ‘leaky gut’

 Physiologic activity:
 Greater particle size promotes peristalsis and reverse persistalsis:
better mixture with enzymes and digestion
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Microbial ecosystem and host defense
 Host defense mechanism: gut barrier function
 Maximize the protective innate immunity
 Prevent inflammatory response, keep a state of oral tolerance

 Complex regulation of the microbial ecosystem:

 Suppress invasion of pathogens ( Salmonella, E. coli)
 Increase diversity in de microflora
 Inhibit overgrowth ( Clostridium perfringens – Clostridiaceae)

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Gut problems since the ban of AGP
 Broilers:
 Coccidiosis clinical and subclinical
 Necrotic enteritis
 Dysbacteriosis - Bacterial Enteritis – bacterial overgrowth

Wet Litter

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Bacterial Enteritis

Clinical signs and necropsy:

- Wet litter (-> pododermatitis)
- Diarrhea
- No increase feed intake
- Water/feed ratio
- Thin, transparent, fragile intestinal wall
- Ballooning intestinal wall
- Undigested feed in distal part gut
- Abnormal intestinal content: too liquid, too gassy, too fat, too slimy
- Inflammation gut wall (much milder than with NE, not necrotic!)
characterised by redness (mucosal and/or serosal) and hyperaemia of
blood vessels servicing gut

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Coccidiosis =main pre-disposing
factor NE and bacterial enteritis!
0. Normal gut with well developed villi
1. Coccidia infecting gut
mucosa, causing villus atrophy
3. Immune reaction and damage
causes plasma protein leakage/
intestinal function decreased, more
nutrients in gut
4. Clostridiaceae (rods) grow on
available nutrients, mucus and plasma
proteins and attach to gut lining,
causing further reaction of immune
system and gut defences (mucus,…)
2. Damaged gut reacts by: villus
fusion, increase of mucus production
Goblet cells and immune reaction
causing inflammation
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BE and Coccidiosis
 Coccidiosis prevention is a key factor to control BE
 Anticoccidials: some also have antimicrobial activity
 Most important is to preserve good anticoccidial efficacy of the
limited products available
 Rotation programs, chemical clean up
 To enhance integrity of the gut, and absorption of nutrients

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Bacterial Enteritis
High feed intake,
high NSP levels, Imbalance microbial
coccidiosis system
1

3
Result: back to 1…. 4

Inflammation and
oxidative stress
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Overview
 Introduction

 Importance of gut health and contributing factors

 Alternative solutions to improve gut health

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Bacterial Enteritis
Reduce feed intake,
limit NSP levels, avoid
coccidiosis, avoid viral
infections
4 or other products for
Optimise anticoccidial
program, use exogenous
enzymes, mycotoxin
binders ….
Suppress bacterial
proliferation (antibiotics,
acids, probiotics, AGP
1 …. )
3 Add beta-glucan/MOS
faster restoration gut
morphology, reduce
inflammation and
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Alternatives to enhance intestinal health
Combination of different products that act in synergy to improve

 Gut barrier management: integrity and recovery of intestine

 Control the microbial ecosystem and the host defence

mechanisms

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Alternatives to enhance gut health
 Improved cox control

 Improved digestibility feed

 Enzymes
 Lower NSP
 Mycotoxin binders

 Alternatives
 Acids
 Pre and probiotics
 Phytonutrients (herbs and essential oils)
 Others: Bacteriophages, Antimicrobial peptides, Toll-like receptor
agonists……….

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Organic Acids
 Antimicrobial activity of the acid depends on
 Chemical structure, chain length SCFA- MCFA
 Form dissocciated or not (pKa value)
 MIC values versus certain pathogens

 Medium Chain Fatty Acids (MCFA)

 C6:0-C12:0 have more antibacterial activity than SCFA
 Caprylic –caproic acid have lower MIC for E. coli and Salmonella
 Lauric acid has a lower MIC for Clostridium perfringens

(Huyghebaert et al. 2011)

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Organic acids
 Originally: SCFA used for general bacterial decontamination of
the feed itself or drinking water
• effective in the crop and gizzard, not in the caeca

 Butyric acid:
• Promotes development and recovery of villi
• Stimulates the expression of the tight junction proteins – claudines
• Limits invasion of pathogens ( E. coli, Salmonella)
• Promotes beneficial microbial ecosystem

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Organic acid
 Butyric acid has a beneficial effect on the gut integrity and the
microbiotic ecosystem but it has to be available in the caeca

 Coated Butyrate by micro-encapsulation (slow release matrix)

Or
 Enhance butyrate producing bacteria in the caeca
• Direct –BA producers( Clostridium clusters IV –XIVa)
• Indirect- Lactobacilli stimulate growth of BA producers (cross-feeding)
(Van Immerseel et al. 2010)

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Probiotics
= Single or mixed cultures of living microorganisms
which beneficially affect the host by improving the
properties of the indigenous microbiota (Fuller 1992)

Mode of action:
 Competition pathogens for adhesion site
 Competition pathogens for nutrients
 Immunomodulation
 Production antimicrobial compounds
e.g. quorum sensing = different populations of bacteria
communicate and influence each other (Boyen et al 2008)

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Prebiotics
= Non digestible food ingredients that selectively favor the
multiplication or metabolic activity of a specific fraction of the
intestinal microbiota (Gibson & Roberfroid, 1995)

Products:
 Inulin + oligofructose/fructo-oligosaccharides (plant roots)
 Mannan-oligosaccharides (yeasts)

Mode of action:
 Β-glucans: immunomodulators
 Mannan oligosaccharides: supports Lactobacillus spp.,
reduction pathogens

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Prebiotics
(1-3,1-6) ß-glucans
 Bind to macrophages
-> activation macrophages
1. Stimulation phagocytosis
 a-specific immunity boost
2. Activation T&B-lymphocytes through
increase cytokine production
 specific immunity boost
mannan oligosaccharides
• Polysaccharide-protein complexes
1. Substrate and energy source for
Lactobacillus spp.
 Enhancement of beneficial flora
2. Competitive bindingsite for certain Gr-
bacteria
 Inhibits attachment Salmonella
spp.and E.coli to the intestinal wall
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Alphamune: effect on gut morphology

• Villus height and villus surface area:

– Increase villus length & villus surface area
 Better digestion and nutrient absorption
 Increased BW, better FCR

Much more epithelial cells available

for nutrient absorption in picture on
the left

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Herbs and essential oils
 Phenolic compounds, glycosides, alkaloïds: derived from
plants
 Carvacrol (oregano) allicin( garlic), cinnamaldehyde(cinnamon)
 Mode of action:
 Effect on tight junctions, anti- oxidant, immunomodulation
 Stimulate the endogenous digestive enzyme

 Large variation in composition:

 Origin, harvest and storage, extraction method
 Cave! Contaminants: mycotoxins, heavy metals

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Alternative approach to gut health

 Stable gut flora => good gut health

-> Save nutrients
-> Less microbial and toxin leakage
-> Minimise reaction immune system
Improved performance

 A lot of research on alternatives: synergistic blends of different

products

 Objective parameters needed to evaluate the effect on gut

health in vitro and in vivo

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conclusion

Now, there has been a great deal of information on

new biocontrol approaches for preventing and treating
bacterial, viral, and parasitic pathogens in food animal
production. Multiple alternatives, including prebiotics,
probiotics, phytonutrients (herbs and essential oils),
hyperimmune antibodies, bacteriophages, antimicrobial
peptides, and toll-like receptor (TLR) agonists, have
already been used by the animal industry for various
claims, but it is generally accepted that none of these
alternatives are known to be as effective as AGP in
field application. However, a combination of additives
(e.g., probiotics and prebiotics) or novel feed additives
have shown some efficacy to compensate for production
loss, in the absence of AGP, with economic returns.

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Thank you!

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