2. REGULATION OF ANTIBIOTIC GROWTH PROMOTERS (AGP) WILL ACCELERATE
2
Source:DuPontinterpretationofregional/countryregulatoryframeworks
Existing ban
AGP regulatory status in leading markets
Existing restrictions
- scheduled ban
No restrictions
Existing restrictions
+ customer-driven
self regulation
3. DUPONT, AS A TECHNOLOGY AND SCIENCE LEADER, IS STRATEGICALLY FOCUSED ON GUT
HEALTH AND ALIGNMENT WITH CUSTOMERS
3April 12, 2018 Training Nutribiosis April 12 Confidential
Building on our extensive,
in-depth understanding of
feed additive applications
Microbiome research
In-field Analysis and Applied
Research, with 80,000 guts
sampled from 500 poultry farms
Advanced omics technology,
In vitro Gut Simulators
Let’s collaborate to make change
4. ANTIBIOTIC-FREE ANIMAL PRODUCTION IS A COMPLEX ISSUE
4
Maintaining consistency is a daily challenge for
live production managers and nutritionists are
overwhelmed by the number of different feed
options to test. There is no silver bullet
Understanding the interaction between the gut
& immune function, microbiome and nutrition
and how new technologies influence this is a
crucial step in this evolution
Unpredictable disease challenges are on the
rise with veterinarians having fewer weapons
to fight them
5. Gut and immune function
NUTRIBIOSIS
IS A STATE DESCRIBING AN INTERACTION
5
Nutrition
Microbiome
8. ANTIBIOTIC-USE SUPPORTED A NUMBER OF CELLULAR FUNCTIONS THROUGH DIRECT AND
INDIRECT MECHANISMS
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• Reduced disease challenge
• Reduced sub-clinical disease
• Reduced outbreaks
• Reduced bacterial dysbiosis events
• Direct signaling with host tissue
• Off-target anti-inflammatory effects
• Lowered biosecurity hurdle
• Better synchronized growth without pathogen challenge
Effects of antibiotics are still
governed by natural physiology and
gut-microbe interactions; therefore,
we can identify natural stability points
through nutrition, gut microbiome,
and host physiology to substitute
effects of exogenous antibiotics.
9. THE UNDERSTANDING OF NUTRIBIOSIS BRINGS
NEW INSIGHTS TO ANIMAL PRODUCERS, ENABLING THEM TO:
9April 12, 2018 Training Nutribiosis April 12 Confidential
Improving
Animal Performance
Promote
Animal Welfare
Improving
Gut Health
Proper decision
making on feed
additives
10. FOCUS ON CASE-STUDIES: RECAPTURING PERFORMANCE FROM
UNFAVORABLE NUTRIBIOTIC STATES
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11. UNFAVORABLE NUTRIBIOTIC STATE
GIT UNDER CHALLENGE (NECROTIC ENTERITIS) Nutrition
High feed intake
High levels of anti-nutritional factors
Poor ingredient quality
High levels of undigested nutrients
Microbiome
Cocci outbreak
Presence of toxin producing C.
perfringens
Low diversity/ imbalance
High levels of protein fermenters
Gut and immune function
Inflammation
Oxidative stress
Reduced surface area
Poor gut function
Ultimately these factors will interact with
each other reducing animal performance:
11
12. Ultimately these factors will interact
with each other reducing animal
performance:
UNFAVORABLE NUTRIBIOTIC STATE
SWINE DYSENTERY
Nutrition
High energy high protein diets
Low nutrient digestibility
Too much or too little carbohydrate
fermentation in the hind gut
Microbiome
Increased prevalence
of Brachyspira hyodysenteriae
Gut and immune function
B. hyodysenteriae induces
extensive inflammation
Necrosis of the epithelial
surface of the caecum and
colon
12
13. ANTIBIOTIC TREATMENTS CAN SUCCESSFULLY TREAT PATHOGEN-DERIVED CHALLENGES,
BUT AT WHAT COST?
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• Antibiotic resistance
• Bacteriophage release and genetic exchange
• No coverage of root cause (potential reservoir of pathogens in the system)
Antibiotic resistance requires multiple
antibiotic treatments and loss of drugs or
classes for use in field
Genes for virulence or resistance can be
quickly passed through to other bacteria
after bacteriophages released
Reservoirs of pathogens can continually
re-infect animals in environment
14. ANTIBIOTICS CAN ATTACK PATHOGENS DIRECTLY, BUT MAY NOT PROVIDE SYSTEMS-WIDE
COVERAGE
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Time
Bacterialchallenge
Normal trajectory of infection
Active infection (toxins, iron capture, cellular destruction)
Active immune response (phagocytosis and cytokine signaling)
Re-alignment of energy resources (Dynamic energy budget)
Understanding nutribiosis can play a part in developing your feeding strategy to
support these host functions during infection, and also help to support natural
recovery post-infection
Distorted microbiome
15. GIVEN THE SUSCEPTIBILITY OF HOST SYSTEMS DURING INFECTION, HOW CAN STRATEGY
COME TOGETHER TO HELP PROMOTE HEALTH AND IMPROVE PERFORMANCE ?
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16. Nutrition
Improved digestibility of starch fat and
protein
Improved nutrient uptake
Improved energy utilization shown by
improved calorie conversion into
growth performance
Improve breakdown of fiber in the diet
FAVORABLE NUTRIBIOTIC STATE
Syncra® AVI
Ultimately these factors will interact with
each other to give positive effects:
Gut and immune function
Improved intestinal integrity and tight
junctions
Improved villi height to maximize
absorptive area
for nutrient absorption
Reduced risk of gut inflammation and
inflammatory response
Reduced physiological stress
Microbiome
Production of prebiotic AXOs
Increased beneficial bacterial
populations such as Lactobacillus
versus non-beneficial populations
Reduced levels of opportunistic
microbes (like coliforms)
Positive changes in fermentation
patterns (increased butyrate production)
16
18. FAVORABLE NUTRIBIOTIC STATE
Syncra® SWI
Gut and immune function
Improved gut barrier
strength through tighter
junctions
Nutrition
Release of fiber bound nutrients
Increased protein digestion and
amino acid utilization
Microbiome
Bacillus adapt to the diet and produce
fiber degrading enzymes to help nutrient
digestion
Reduction in undigested proteins so less
substrate for non-beneficial bacteria
Production of prebiotic AXOs
Reduced protein fermentation so less
ammonia produced
Increase in Lactobacillus populations,
indicating a beneficial shift in the
microbiota
Increase fiber fermentation resulting in
higher SCFA (e.g. butyrate).
Ultimately these factors will interact
with each other to give positive effects:
18
20. DUPONT PRODUCTS PROVEN TECHNOLOGIES FOR MAXIMISING NUTRIENT DIGESTION, GUT
HEALTH AND PERFORMANCE
Microbial modulation
Maximised nutrient digestibility
Improved intestinal integrity
Immune response modulation
DuPont enzymes
Improved digestibility and
performance
Improved flock uniformity
Flexibility on ingredient
use
DuPont probiotic
Protection against health
challenges
Accelerated immune
development
Proven efficacy on >500 farms
21. ARABINOXYLANS ARE IN BOTH SOLUBLE AND INSOLUBLE FRACTIONS OF THE CELL WALL
4.48%
3.62%
3.02%
6.51%
1.50%
0.37%
0.76%
1.17%
Wheat Corn SBM Corn DDGS
Ins. Arabinoxylans S. Arabinoxylans
Different raw materials have
different arabinoxylan
composition
21
22. TOTAL ARABINOXYLAN (TAX) LEVELS IN BROILER DIETS IMPACTS PERFORMANCE
Trialcode:XAP0910;
XAP1408;XAP1409
1.73
1.70
1.83
1.75
1.54
1.54
1.59
1.55
1.591.57
1.55
1.51
y = 0.4669x + 1.0021
R² = 0.60
1.4
1.5
1.6
1.7
1.8
1.9
1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8
FCR 42d
TAX:ME (kg/kcal*10-4)
Impact on increasing levels of TAX in diets on performance in broilers*
*Combined data of positive and negative control diets without addition of enzymes, TAX calculated with decision tree calculator divided ME of diet for normalization
22
23. MOVING FORWARD IN GUT HEALTH STRATEGIES
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Where are you leveraging your production system
based on feed and performance?
How is your strategy providing coverage to not only
gut tissue, but also the immune system?
Changes to the microbiome can happen fast and may
not self-correct, how can you stabilize against a
stressed system?
***ONLY READ FIRST PARGRAPH – REST IS BACKGROUND INFO***
There has never been a more urgent need for this understanding. The rise of antimicrobial resistance combined with increasing global pressure to reduce or remove antibiotics from the food chain is driving fundamental change within the animal production industry; creating new challenges and heightening demand for viable alternatives.
Existing Ban: EU, Thailand, Russia, S. Korea, Australia. Note: therapeutic use of antibiotics is not curtailed.
Existing restrictions: China, US, Canada, NZ: no “ban” but the products can only be used under veterinary supervision and/or to treat disease (i.e. quasi ban). i.e. growth promotion claims have been removed and prescriptions are required for use in animals, but it’s not called a “ban”.
Latam: regulated as veterinary products – can be registered, but the situation is that all LATAM is migrating to ban the use as growth promotersScheduled ban: Vietnam ban scheduled for 2019 – pending and may change but currently scheduled.
No restrictions: Malaysia, Philippines
Drivers of regulation:
Antimicrobial use in livestock is primarily associated with the routine use of antimicrobials as growth promoters or their inappropriate use as low-cost substitutes for hygiene measures that could otherwise prevent infections in livestock.
In 2016, the UN recognized the inappropriate use of antimicrobials in animals as a leading cause of rising anti-microbial resistance. Causes of AMR:
The primary driver for the accumulation of harmful resistance genes in the animal reservoir is the large quantity of antimicrobials used in animal production.
since the biomass of animals raised for food exceeds by far the biomass of humans, new resistant mutations are more likely to arise in animals.
Drivers of customer driven self regulation:
Consumer groups are beginning to demand action on antibiotic use. For example, in the USA: McDonalds, Chick Filet all publicly committed to going anti-biotic free.
Advocacy opportunities:
Regulators are struggling with how to regulate traditional feed additive type products with drug-like claims.
We see more and more associations/regulatory/quasi-govt bodies talking about this issue
We need to be active in our advocacy efforts, provide regulators with the information they need.
Why DuPont? As leaders in both enzyme and gut health technologies, DuPont is breaking open the “black box” of nutribiosis, leveraging our microbiome research, our in-field analysis and applied research of over 80,000 guts sampled from over 500 farms, advanced omics technology and in vitro gut simulators, as well as continuing to build on our extensive, in-depth understanding of feed additive applications.
DuPont Why – DuPont exists to collaborate with customers to make positive change
Without the antibiotic line of defense, animal production becomes more of a complex issue, as unpredictable and diverse disease challenges are on the rise, with veterinarians having fewer weapons to fight them. Maintaining consistency is a daily challenge for live production managers and nutritionists are simply overwhelmed by the number of different feed alternatives to test. All recognize that there is no silver bullet. So understanding the interaction between the gut and immune function, microbiome and nutrition, and how new technologies like ways to measure this interaction influence this, is a crucial step in this evolution.
We have seen that when it comes to evaluating the impact of any nutritional intervention on animal health, there remains significant room for improvement. Current tools for measuring feed additive efficacy are still heavily relying on traditional feed and weigh metrics, such as feed conversion ratios (FCR) and average daily gain (ADG). However, to properly measure nutribiosis, producers need additional scientific measurements on site which take into account a multi-disciplinary approach to demonstrating added value. At DuPont, we are committed to improving these tools.
Nutribiosis is the state describing the interaction between nutrition, microbiome and gut & immune function.
Now let’s look at why the interaction is important. These functional areas – nutrition, microbiome and gut and immune function are not new, however looking at them together in a holistic way and understanding how they interact and impact each other is crucial and what makes nutribiosis different from other gut health concepts in the market.
It is based on 3 principles:
Firstly, we need to get nutrition right to ensure that the animal has all the nutrients needed to reach its full potential. It is also important to either limit the amount of undigested nutrients or control the types of undigested nutrients that reach the terminal ileum, so that we are not providing substrates for the non-beneficial bacterial populations to feed and thrive on. Secondly, having a microbiome which is diverse, where beneficial bacteria outnumber non-beneficial bacteria, and possible opportunistic pathogens are kept under control is key. This avoids the occurrence of sub-clinical and clinical disease challenges that would otherwise reduce overall performance and profitability. Finally, a well-developed gut structure and high-functioning immune system are vital to allow animals to maximize nutrient absorption and deal with challenges when they occur - whether they are bacterial, viral or environmental. Any immune response mounted by the animal uses energy and can negatively impact growth if the immune response is sustained or uncontrolled.
*Microbiome: is the population of microorganisms located in a specific organ, in this case GIT. Microbiome covers everything the microbiota is doing; where microbiota is the microbes which are present and microbiome is the entire capability of the microbiome.
A Favourable nutribiotic state is what we consider as good intestinal health
The trinity equilibrium is fragile and can also be disturbed by external and unpredictable factors, i.e. climate, temperature, virus.
That’s the reason why gut health additives should always be added in the background to secure the equilibrium.
Nutribiosis is a state
And as such
It can be favourable or unfavourable
In the case of an unfavourable nutribiotic state, we see an imbalance between the 3 pillars: nutrition, microbiome and gut & immune function.
This imbalance results in poor intestinal health and suboptimal performance.
The equilibrium between the three pillars of nutribiosis is fragile and there are many external factors that could make it go off balance. This typically leads to a vicious cycle from which the animal or its performance may never fully recover.
It’s crucial because this understanding of nutribiosis brings new insights to animal producers, enabling them to improve gut health and make more profitable decisions, leading to improved animal performance and welfare.
So lets look at some case studies involving unfavorable nutribiotic states that were generated by infection. Traditionally these may currently or were once treated by simple antibiotics, but the overall interactions were not limited to bacteria causing infection.
The example of an unfavourable nutribiotic state for broilers that we have chosen is Necrotic Enteritis.
Necrotic enteritis is a condition which arises from a combination of an intestinal challenge and an overload of nutrients in the latter part of the intestinal tract
The intestinal challenge can be caused by coccidiosis, this combined with high levels of undigested protein (as a result of high levels of feed intake, or high levels of antinutritional factors) can result in an outbreak
The outbreak is caused by an opportunistic pathogen, Clostridium perfringens – which thrives on undigested nutrients
C. perfringens causes intestinal damage through the production of toxins, reducing gut function by reducing the surface area for absorption of nutrients
Which in turn creates more feedstuffs for the bacteria – it is for this reason that we consider necrotic enteritis to be a vicious cycle
Ultimately these interactions between nutrition, microbiome and gut and immune function result in suboptimal animal performance
The example of an unfavourable nutribiotic state for pigs that we have chosen is Swine Dysentery.
1. High energy high protein diets are associated with swine dysentery as well as low nutrient digestibility and too much or too little carbohydrate fermentation in the hind gut
2. Combined with poor management practices nutritional factors can cause increased prevalence of Brachyspira hyodysenteriae, a causative agent of swine dysentery.
3. B. hyodysenteriae induces extensive inflammation and necrosis of the epithelial surface of the caecum and colon
Ultimately these interactions between nutrition, microbiome and gut and immune function result in suboptimal animal performance
Ref…http://www.mdpi.com/1660-4601/10/5/1927/htm
To illustrate the positive nutribiotic state we have looked at 3 examples from our product portfolio and how those 3 products can result in a positive nutribiotic state. These are examples only and other products could also be used.
The first product we will look at is Syncra® AVI, a product developed for health effects, and how it positively influences nutrition, the microbiome and gut and immune function.
Firstly lets consider Gut and immune function. Studies have shown that Syncra® AVI:
Improved intestinal integrity and tight junctions leading to less risk of foreign materials such as microbes crossing between the gut cells and into the blood.
Improved villi height to maximise absorptive area for nutrient absorption
Reduced risk of gut inflammation and inflammatory response following challenge indicating the animal recovers quicker
Reduced physiological stress demonstrated by reductions in acute phase protein levels following challenge.
If we now look at nutritional effects of the product, in trials we have seen:
Improved digestibility of starch fat and protein meaning less undigested substrate reaching the terminal ileum where it can act as food for non-beneficial bacteria
Improved nutrient uptake
Improved energy utilisation shown by improved calorie conversion into growth performance
Improve breakdown of fibre in the diet
Finally lets consider the effects on the microbiome:
The product contains xylanase which results in production of prebiotic AXOs
Increased beneficial bacterial populations such as Lactobacillus versus non-beneficial populations
Reduced levels of opportunistic microbes (like coliforms). Less undigested protein reaching the terminal ileum means less substrates for protein fermenters like Clostridia.
Positive changes in fermentation patterns, illustrated by increased butyrate production in in vitro studies
Next we will look at Syncra® SWI, a product developed for performance improvement, and how it positively influences nutrition, the microbiome and gut and immune function.
First looking at gut and immune function trials, we have demonstrated improved gut barrier through tight junctions – reducing the risk of materials passing between the gut cells and causing an immune response.
Second, considering the nutritional effects the product has been designed and proven to release fibre bound nutrients and increase protein digestion and amino acids utilization resulting in better growth of the animal and better carcass characteristics such as increased lean meat deposition. Increased protein digestion means less undigested protein reaching the hind gut of the animal.
Finally, looking at the microbiome, we have seen a number of benefits with the product:
Bacillus adapt to the diet and produce fibre degrading enzymes to help nutrient digestion
Less substrate for non-beneficial bacteria due to the better digestion seen with the product
Production of prebiotic AXOs due to the fibre degrading enzymes produced by the Bacillus
Reduced protein fermentation so less ammonia produced
Increase in Lactobacillus populations, indicating a beneficial shift in the microbiota
Increased fibre fermentation resulting in higher SCFA (e.g butyrate).
The Syncra® AVI product combines enzyme technology for breaking down antinutrients and improving nutrient digestibility and probiotic technology for improving gut health, creating a new benchmark for optimizing gut health and maximising performance. With this combination we have demonstrates effects on digestibility, the microbiome, as well as intestinal integrity, gut structure and immune responses.
Arabinoxylans are polysaccharides formed by a backbone made of xylose and branched arabinose (sugar monomers). This polysaccharide is the main NSP (non starch polysaccharide) in corn and wheat and is part of the fiber in most of the vegetable raw materials.
Its degree of branching and polymerization (DS, DP) gives arabinoxylans different behaviour in water. More branched and bigger polymers (higher DS and DP) are usually insoluble in water and cause the boxing effect by acting as a barrier to the animal’s endogenous enzymes. While smaller polymers are water soluble but increases the digesta viscosity reducing the absorption rate of nutrients during digestion.