U.S. strategies & research on antibiotic alternatives in swine diets

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1 U.S. strategies & research on antibiotic alternatives in swine diets Dari C. Brown, PhD Sr. Director, Technical Solutions Purina Animal Nutrition, a Division of Land O Lakes Inc. USA dcbrown@landolakes.com

2 Antibiotics (AB) Use in Animal Agriculture Sub-therapeutic levels of antibiotics to livestock since 1940 s Subtherapeutic < 200g/ton of feed enhance production performance Therapeutic treatment and prevention of disease Greatest growth-promoting effect in young pigs Phase Control AB Benefit (%) Starting (7-25 kg) Daily gain (kg) Feed/Gain Growing (17-49 kg) Daily gain (kg) Feed/Gain Grow/Finish (24-89 kg) Daily gain (kg) Feed/Gain Cromwell, Antibiotics 2001 Use in Swine Feed, USDA 1999 Response depends on facilities and management 2

3 Antibiotic Controversy in Animal Agriculture 2006 Ban on use of growth-promoting antibiotics in the EU nations 2017 US Implementation of Guidance 213 by FDA, requiring a 3 Veterinary Feed Directive (VFD) for all therapeutic uses of medically-important antimicrobials intended for use in animal feed. NEW RULE.allows use of these such antibiotics in foodproducing animals for prevention, control and treatment of specific diseases under supervision of a licensed veterinary...but they can NO longer be used for growth promotion, increased performance & feed efficiency.

4 Following drugs became Veterinary Feed Directive (VFD) drugs as of 1/1/17: Apramycin (not marketed) Avilamycin (already VFD) Chlortetracycline Erythromycin (not marketed) Florfenicol (already VFD) Hygromycin B Lincomycin Neomycin (not marketed alone) Oleandomycin (not marketed) Oxytetracycline Penicillin (approval withdrawn) Sulfamethazine (not marketed alone) Sulfadimethoxine/Ormetoprim Sulfamerazine (not marketed) Tilmicosin (already VFD) Tylosin Virginiamycin Consumer awareness (US) is causing some restaurants & retailers to develop policy or make pledges to eliminate, or restrict certain uses of, antibiotics in their meat supply chains. Opportunity to: 1. Refine our biosecurity & management practices 2. Refine how antibiotics are used in our operations as well as review our feeding programs & explore alternative compounds with similar modes of action to elicit a response. 4

5 Alternative feeding strategies to replace application of antibiotic growth promoters in pigs Feeding Program: Optimal Nutrition for stage of growth 5 Dietary Make Up: Ingredients Quality Digestibility Nutrient content Amino Acids levels/ratios Lactose levels Protein/energy/etc Pharmological levels of Zn & Cu Feed Additives/Technologies: Plasma, bioactive peptides, Probiotics (Lactobacillus, Bacillus, Live Yeast, etc. ) Phytogenics (Herbs/Spices/EO) Prebiotics (Inulin/YCW/Betaglucans/MOS/FOS/GOS) Nucleotides Fatty Acids (SCFA (4-6 C)/MCFA (6-12C)) Bacteriophages, vaccinations, egg AB Bacterioncins Enzymes

6 Alternative nursery feeding programs (complex vs less complex) with & w/o antibiotics on nursery pig performance Nutrient Complex <Complex TRTs (d 0 to 36 postweaning (PW); weaning at 19 d of age): Protein, % Complex diets (4 phase feeding program) Dig Lysine, % As 1 but w/o AB Lactose, % 3. Less Complex (3 phase feeding program) +33% 4. As 3 but w/o AB Energy, vitamins, trace minerals = = Ingredients Note: Antibiotic=Aureomix (10 lb/ton) Oats, % +33% 17 pens/trt (4 or 10 pigs/pen); 440 pigs total Plasma, % +90% No water medication was used throughout the experiment SBM, % -28,8% Both programs included several feed additives (such as palatants, pro- & prebiotics, Highly digestible nutraceuticals, proteins organic acids, yucca, pharmological +32% levels Zn & Cu) LOL-PS1055; 2016

7 Alternative nursery feeding programs (complex vs less complex) with & w/o antibiotics on nursery pig performance Feed Prog Antibiotic Day 0-7 ADG, kg ADFI, kg Day 0 21 ADG, kg ADFI, kg Feed:Gain N= 440 pigs, 17 pens/trt (4 or 10 pigs/pen) 7 Complex - Complex + <Complex - <Complex + SEM Feed Prog P-value AB Feed Prog* AB LOL-PS1055; 2016

8 Alternative nursery feeding programs (complex vs less complex) with & w/o antibiotics on nursery pig performance Feed Prog Antibiotic Day ADG, kg ADFI, kg Feed:Gain Day 0 36 ADG, kg ADFI, kg Feed:Gain N= 440 pigs, 17 pens/trt (4 or 10 pigs/pen) 8 Complex - Complex + <Complex - <Complex + SEM Feed Prog P-value AB Feed Prog* AB LOL-PS1055; 2016

9 Alternative nursery feeding programs (complex vs less complex) with & w/o antibiotics on nursery pig performance Feed Prog Antibiotic Weight, kg Initial Day Day Day Complex - Complex N= 440 pigs, 17 pens/trt (4 or 10 pigs/pen) + <Complex - <Complex + SEM Feed Prog P-Value AB Feed Prog* AB Summary: The 1.17 impact kg of AB was greater 0.40 kg Complex in Phase vs 3 <Complex and the response seems to be greater in Less Complex feeding programs kg 1.41 kg AB vs No AB

10 Mode of action of antibiotic feed additives Improved Performance Favorable shift/modification intestinal microbial populations (stimulation/inhibiting) Enhanced nutrient absorption & utilization Modulation of immune cells (less immune defense) Alters growth factors/hormones (ex. increased protein accretion) 10 Allen et al., Trends in Microbiology, 2013

11 Mode of action of Probiotic, Prebiotic & SCFA Probiotics Nutrient & prebiotic competition Prebiotic Balanced Microflora fermentation SCFA Lumen X Competitive exclusion Immune stimulation Intestinal epithelial DC DC T T Energy Improved gut morphology (villi & crypt development, tight junctions and mucin production) Treg B T B B 11 Cytokine regulation Metabolic regulation

12 Antibiotics Organic acids Probiotics: Comparative efficacy in piglet feeding Number of studies % change growth rate % change FCR Antibiotics Carbadox Olaquindox Avilamycin Organic acids (SCFA) Formic acid Sorbic acid Fumaric acid Citric acid* Other org. acids Formiates Combinations Probiotics Lactic acid bacteria Bacillus bacteria (Freitag et al. 1998; *Partanen, 2001) 12

13 Mode of action of activated MCFA GUT MICROBIOME BALANCE Highly antimicrobial drjockers.com 13 GUT IMMUNITY Reduced pathogen virulence IMPROVED NURSERY GAINS & FEED CONVERSION GUT DEVELOPMENT & REPAIR GUT DIGESTION & ABSORPTION myremedy.co.nz/leaky-gut/ Improved morphology

14 Effect of SCFA & MCFA on specific bacterial strains & invasion of Salmonella Bacterial strain Propionic acid MIC (g/kg) Butyric acid Formic acid Lactic acid MCFA* Aspergillus niger >10 >10 >10 > Bacillus cereus >10 >10 > Campylobacter jejuni Clostridium perfringens 5 > Enterococcus faecalis >10 >10 > Enterococcus faecium >10 >10 > Escherichia coli >10 >10 > Salmonella enteritidis >10 >10 > Staphylococcus aureus 5 >10 > Brachyspira hyodysenteriae MIC-values: comparison with other acids (Houf, 2005) 14 >10 >10 >10 > Streptococcus suis 1.25 Boyen, 2008

15 The effects of feeding activated MCFA on nursery pig performance 15 Criteria* Nursery Program (NO MCFA) Nursery Program (0.2% MCFA* in PH1/PH2 & 0.1% in PH3/PH4) Initial Wt, kg Improvement Day 27 Wt, kg kg Day 41 Wt, kg kg D 0-27 ADG, kg b a 11,1% ADFI, kg FE a b 5,2% D 0-41 ADG, kg b a 8,9% ADFI, kg FE b a 4,38% ab Means in the same row with different superscripts differ P < 0.10 *11 pens/trt (20 pigs/pen); Budget: PH1: 1.13 kg, PH2: 2.27 kg, PH3: 5.44 kg, PH4: kg; 41 days PW; weaning 19 days of age) *Aromabiotic-MCFA=mixture of activated MCFA

16 Phytogenic components have been used in traditional medicine for digestive disorders, benefits include: Antioxidant properties Reduced fatty acid oxidation & Improved cell integrity Increased intake Appetizer or Flavoring agent Improved gut function & nutrient uptake Stimulates for increased gastric juice & bile secretion to support nutrient digestion Anti-inflammatory & Antimicrobial properties Reduced intestinal microbial load & Reduced pathogenicity Improved Performance Hashemi and Davoodi, (2011) 16 16

17 Phytogenics: active substance categories Essential oils Oregano oil Peppermint oil Pungent subst. Black pepper Chili Garlic Bitter subst. Wormwood Milfoil Hop Vermouth Flavonoids Citrus fruits Primrose Saponins Yucca Quillaja Tannins Chesnut Wine grapes Chesnut Mucilage subst. Lindseed Fenugreek Flee worth 17 17

18 Feed conversion ratio improved by 1 4 % 18 Franz et al. (2010)

19 Phytogenics and antibacterial effects (MIC values mg/l) E. coli Salmonella thyph. Staph. aureus Listeria monocyt. Rosemary > Sage Oregano Thyme Clove > Lemongrass Carvacrol ,5 Thymol Geraniol Eugenol Franz et al, (2010)

20 Effect of combination Phytogenic Product (CPP) with or without AB on Pig Final Body Weight ,9 % % + 1,7 % ,6 % Initial BW of 6.56 kg *CPP effect (P < 0.05) 20 neg. Control CPP* AB** AB**+CPP* 20 *CPP=200 ppm phytogenic product (Fresta F) = combo of onion oil, garlic oil, peppermint oil, psyllium seed husk, chamomile flowers, etc. **AB = Phase 1; Mecadox-10 (25 ppm), Phase 2 & Phase 3; Medi-Flex 250 (Chlortetracycline, Sulfathiazole & Penicillin; 50 ppm) Phase1: 7 d, Phase2: 14 d, Phase3: 14 d (35 d post-weaning (weaning d 19 of age)) 72 pigs (21 days of age; 6.57 kg BW); 3 pigs/pen; 6 pens/treatment. LOL, 2000

21 Example on efficacy of essential oils in piglets changes relative to control (%) Weight gain Feed intake Feed conversion ratio Control Essent.Oils Antibiotic Essential oils in piglets (carvacrol, thymol, anethol, limonene) (Kroismayr et al. 2007) 21 21

22 Essential oils in piglets (carvacrol, thymol, anethol, limonene): Reduced colony counts at distal ileum Log(CFU/g gut content) p < 0.05 p < 0.05 Aerobic bacteria, sum Control Essent.Oils Antibiotic Anaerobic bacteria, sum 22 (Kroismayr et al. 2007) 22

23 Synergism is the key Organic Acids Phytogenics MCFA 23

24 Combination Technologies (CT*; Proprietary blend of key extracts & acidifiers) as an alternative to antibiotic growth promoters on nursery pig performance 24 Nursery Program AB* + 0.1% CT** Nursery Program NO AB % CT** Mortality # 7 2 Start Wt, kg Day 22 Wt, kg Day 50 Wt, kg Day 0-22 ADG ADFI F/G Day 0-50 ADG ADFI F/G total pigs; 22 pigs per pen with 11 replicates Budgets were 4.53/4.53/9.07 phases 1-3 & phase 4 was fed to completion of trial *Medication: Phase 1 DEN/Phase, Phase 2 CTC+DEN, Phase 3 Non-Med /Phase, Phase 4 CTC+DEN (No water Meds used) **OutPace Feed Technology = Proprietary blend of key extracts & acidifiers Commercial Trial-FT145N; 2015

25 Alternative feeding strategies to replace application of antibiotic growth promoters in pigs Feeding Strategies (Complexity of diets) Organic acids Probiotics Phytogenic products Used in combo* May pose an alternative approach & viable option for producers wanting to raise pigs without antibiotics, or reduce the need to use antibiotics at proper hygiene *Other feed technologies might also be viable options that were not discussed today in depth and management 25 25

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