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TRANSCRIPT
Supporting immune function in a post-antibiotic world
Doug Korver
University of Alberta, Edmonton, AB Canada
Western Poultry Conference 2018
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Demand for poultry products• Chicken will surpass pork as the most
consumed animal protein in 2021
OECD (2015), Per capita meat consumed in the world, in OECD-FAO Agricultural Outlook 2015, OECD Publishing, Paris.http://dx.doi.org/10.1787/agr_outlook-2015-graph94-en
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Increasing demand for poultry products
• Growth in meat and chicken consumption will come mainly in the developing world
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The opportunity for nutritionists• Feed represents 70% of the cost of production
– Large potential impact • On overall efficiency, economics, environmental impact
• How we provide the nutrients• How efficiently the birds use the nutrients
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Helander & Fandriks, 2014
Human digestive tract surface area:~32 m2
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What do antibiotics do?• Reduce interactions between host and
microbiome– Reduce microbiota complexity
• Reduce changes in microbial populations
– Reduce inflammation (local and systemic)
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Roura et al., J. Nutr. 1992 122:2383-2390
ANSC 463
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Antibiotic replacements• What are we actually trying to do?• Replace “antibiotics”
– Antibiotics (from ancient Greek αντιβιοτικά, antibiotiká) are a type of antimicrobial drug used in the treatment and prevention of bacterial infections. (Wikipedia)
– An antimicrobial is an agent that kills microorganisms or stops their growth
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Antibiotic replacements• Is copper an antibiotic?
Festa & Thiele, 2012
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Antibiotic replacements• Antibiotic replacements need to be evaluated
carefully– Potential for development of resistance
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Antibiotic replacements• Dietary products that modulate the
microbiome
• Dietary products that modulate host immune response
• Vaccines
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Probiotics – Competitive Exclusion• Example – Lactobacilli
– form a “biofilm” on the crop epithelium
Fuller & Brooker. 1974. American Journal of Clinical Nutrition 27:1305-1312.
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Probiotics – Competitive Exclusion
http://www.aquafeed.com/read-article.php?id=2322
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Probiotics – competitive exclusion• Can work, but can be difficult
– Heat stability (pelleting)– Persistence of effect– Complex > simple
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Prebiotics• Indigestible by the bird• Digestible by specific classes of commensal
microbes– Competitive advantage against bacteria that can’t
digest the prebiotics• Pathogens
• “Feeding the good bacteria”
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β-glucans• Barley, oat, yeast
– Immune system stimulation
• ???
– Other effects (other components of “β–glucan” products)?
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Oligosaccharides• Mannanoligosaccharides
– Derived from yeast
• Fructooligosaccharides– From plants
• Fructose chains
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"MOS MOA" by Julia FitzPatrick - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons -http://commons.wikimedia.org/wiki/File:MOS_MOA.jpg#mediaviewer/File:MOS_MOA.jpg
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Salmonella reduction in vitro
Ricke, Korver et al. Unpublished
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Nucleotides & Nucleosides
http://en.wikipedia.org/wiki/Nucleoside
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Hancock et al., 2012 Nature Reviews Microbiology 10, 243-254
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Organic Acids• Weak acids
– Do not dissociate completely in water
– Formic– Acetic– Propionic– Butyric– Lactic– Citric
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Organic Acids
http://www.thepoultrysite.com/articles/2433/control-of-salmonella-in-poultry-nutrition-by-means-of-organic-acids
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Essential Oils• Aromatic oily liquids from various plants
– Secondary plant metabolites– Low boiling points – Associated with herbs and spices
Brenes & Roura, 2009
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Essential Oils
Lee et al., 2004
• Minimum inhibitory concentration (ppm) of essential oils against various broiler pathogens
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Enzymes• Soluble non-starch polysaccharidases
– Reduce digesta viscosity, effects on microbes
• Degrade specific bacterial components– Β-mannans– Proteoglycans– Flagellin– Others?
• Triggers for immune response, or molecules essential to specific microbe survival or growth
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Immunomodulation• Adjustment of the immune response to a
desired level– Immunopotentiation– Immunosuppression– Induction of immunologic tolerance
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier
• What is “Nutritional Immunomodulation”?– Using nutrients to accomplish the above
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Nutritional Immunomodulation• What is it not?
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• What do we know about the immune system?
Nutritional Immunomodulation
– Unintended consequences
– What is helpful under one set of circumstances may be harmful under others
– Are we smart enough to figure this out?
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Diet n-3 PUFA and Rodent SurvivalChallenge Survival Challenge SurvivalBacterial Viral
Pseudomonas aeruginosa ↔ ↓ Cytomegalovirus ↔Klebsiella pneumonia ↑ Murine leukemia virus ↔↑Staphylococcus aureus ↑ Influenza ↔Salmonella typhimurium ↔ ↓ ↓ Protozoa
Bacteroides fragilis ↓ Plasmodium yoelii ↑Streptococcus Group B ↑ Plasmodium berghei ↑Listeria monocytogenes ↔↓↓↓GI flora (undefined) ↑ ↑
Anderson & Fritsche, 2002
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Nutritional Immunomodulation• Why?
– Innate immunity• Antibiotics
– Performance– Food safety
– Adaptive immunity• Vaccinations
– Optimize response, persistency
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Nutritional Immunomodulation• Examples
– n-3 PUFA– Vitamin E– Carotenoids– Selenium– HyD
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Fatty Acids• n-3 PUFA
– Increase innate immune function• Pro-inflammatory cytokines
Sijben et al, 2003
– Decrease systemic effects of inflammationKorver et al., 1997
– Increase antibody responseSijben et al, 2000
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Body Weight Gaina
030
32
34
36
38
40
Corn Oil Fish OilControl Lofrin Control Lofrin
a
b
aba aa
a
g/ch
ick/
d
Non-infected Eimeria-infectedOil P<.06; Lofrin P<.04; Diet X Eimeria P<.05 Korver et al., 1997 Poult. Sci. 76:1355-1363
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Histopathology
0
0.5
1.0
1.5
2.0
2.5
Non-infected Eimeria-infected
Control Lofrin
Corn Oil Fish OilControl Lofrin
Lesi
on S
core
cc
c
b b
c
ab a
Diet X Lofrin X Eimeria P<.02 Korver et al., 1997 Poult. Sci. 76:1355-1363
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Serum IL-1 Activity3
2
1
0
Stim
ulat
ion
Inde
x
0.07 0.33 0.66 1.00Dietary n-3:n-6 PUFA ratio
a aab
b
P<.003
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What Immunomodulation Can Do• “Nudge” the immune system in the right
direction
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What Immunomodulation Can’t Do• Over-ride immunological
tolerance– e.g. S. enteritidis in laying
hens
Guard-Petter, 2001
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Implications• First, understand what the problem is• Then look at what nutrient(s) may be able to
nudge the immune system in the “right” direction
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Implications• The best approach is probably multifactorial
– Good husbandry– Optimize nutrition effects on immunity
• What is most likely to be “optimal”?
– Prevent interaction of pathogens with the immune system
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Summary• The industry needs to identify suitable
antibiotic replacements– Performance– Welfare– Food safety
• No single product is likely to be effective
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Summary• Need to be aware of the potential for
microbial resistance
• Consumer acceptance
• Efficacy
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