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GREENCAB 70 COATED

GREENCAB 70 COATED. CALCIUM BUTYRATE. PHYSIOLOGICAL EFFECTS. STARCH. FIBRE. PECTINS. FRUCTOSE. PENTOSE. GLUCOSE. 3 P GLYCERALDEHYDE. SUCCINATE. PYRUVATE. ACETYL CoA. PROPIONATE. ACETATE. BUTYRATE. Volatile Fatty Acids (VFA) : Final metabolites of gut fermentation .

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GREENCAB 70 COATED

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  1. GREENCAB 70 COATED CALCIUM BUTYRATE PHYSIOLOGICAL EFFECTS

  2. STARCH FIBRE PECTINS FRUCTOSE PENTOSE GLUCOSE 3 P GLYCERALDEHYDE SUCCINATE PYRUVATE ACETYL CoA PROPIONATE ACETATE BUTYRATE Volatile Fatty Acids (VFA) : Final metabolites of gut fermentation • Butyrate is a normal component of digestive content

  3. VFA PROPORTION DEPENDS ON THE SPECIES • Butyrate is found in all kind of animals gut • It is naturally produced but at lower levels compared to acetate and propionate. • Feed supplementation can be interesting % fatty acid in colon

  4. Ca butyrate CALCIUM BUTYRATE Calcium 2 butyrates are linked with 1 calcium (CH3-CH2-CH2-COO)2-Ca Calcium butyrate salt is less soluble than the sodium salt due to molecula size

  5. GREENCAB 70 COATED ORGINAL PARTICLE PRESENTATION (+/- 1mm diameter) VERY FEW DUST IN ENVIRONMENT COMPARING TO COMPETITION PRODUCTS

  6. GREENCAB 70 COATED CONCENTRATIONS : • GREENCAB 70 COATED IS THE MOST CONCENTRATED FORM OF COATED BUTYRATE ON THE MARKET

  7. GREENCAB 70 COATEDCoating confers intestinal absorption Triglycerides Low lipolytic activity in stomach Triglycerides unsoluble and undigestided in stomach Butyrate salts Coated butyrate reach intestine unmodified STOMACH Butyrate salts Lipase and bile salts action destroy the triglyceride coating Butyrate salts are slowly solubilised in the intestine Butyrate salts INTESTINE

  8. Golgi- apparatus protein chain GREENCAB 70 COATED EFFECT ON CELLS FUNCTIONS Histones 1/ Effect on the nucleus • BUTYRATE is a major modulator of cell metabolism • BUTYRATE induces apoptosis hyperacetylation Changes in histones DNA Modified nucleus transport gene expression processes mRNA 2/ Consequences on cell synthesis Changes in chromatine Enhanced protein structure (enzyme, hormone) synthesis Changes in cell 3/ Consequences on cell activity and exchanges Enhanced morphology and hormone membrane compounds secretion rRNA ribosome Modification in cytoskeleton assembly

  9. GREENCAB 70 COATED Mode of Action • Biochimical and physiological effects • - Developement and protection of intestinal mucosa and villi (absoprtion, enzyme synthesis) • Energy for enterocytes (metabolism) • - Insuline production (villi, Ingestion) Microbiological effects - Normal microbism : positive development - Pathogen flora : Inhibition of : E. coli, Clostridium, Salmonella, Campylobacter…(Streptococcus S.) Semi therapeutical effects - Intestinale chronic inflammation (ref. Theory on GM – Niewold) - Immunity modulation: health vs growth (Saëman, Klaasing)

  10. Effect on Villi-growth Effect of Calcium-butyrate on the intestinal wall (Prof. R. Claus – University Hohenheim - 2004) Control Butyrate Cut from Jejunum : mitosis and apoptosis influence by butyrate

  11. BUTYRATE effect on electric resistance of enterocytes • Anti-inflammatory indomethacine reduces ER • Butyrate avoids the negative effect of Indomethacine

  12. Stimulation of enzyme activity in the intestine by butyrate in piglet (GREENCAB 70 COATED ) 15.2 57.6 63.6 139 11.6 23.7 Micromol Glucose per mg mucus /hour (Pletcher 1991, Newbold, 1991, Butler, 1991)

  13. Nutrient Digestibility in poultry, butyrate effect M.Lippens & G. Huyghebaert -2004 Relatively compared to control group • Butyrate significantly increases nutrient digestibility and utilisation of broiler diets,

  14. Mineral Digestibility in layer, butyrate effect G. Huyghebaert – 2009 (Ilvo-Institute Belgium) GREENCAB 70 COATED at 750 gr/T GREENCAB 70 COATED increases Ca and P digestibility

  15. Stimulation of pancreas enzymes in calf by BUTYRATE GASTRIC JUICE PROTEASES AMYLASE

  16. GREENCAB 70 COATED in broilers : effect on litter quality M. Lippens & G. Huyghebaert (2004) - CLO-DVV • State research station in Belgium. In one performance trial, litter dry matter content has been measured. • Floor pen trial : 4 (12) treatments with 6 replicates and 30-32 birds per pen. Day 0-42. • OUTCOME * All treatments resulted in lower litter moisture than the negative control group. * GREENCAB 70 COATED gave dryer litter than avilamycin

  17. IMPORTANCE OF THE ENTERIC NERVOUS SYSTEM • Gut is highly innervated, able to have autonomous functions • Control gut movement • Fluid exchange • Blood flow • Relationship with central nervous system

  18. GREENCAB 70 COATED :effect on intestine efficacy and growth Direct effect: Maturation effect of butyrate : Increase nutriment absorption and intestinal enzymes secretion Undirect effect: VIP, Neurotransmistors signal intestine  Pancreas Exocrine pancreas : Enzyme synthesis Increase pancreatic enzymes production Endocrine pancreas : hormon synthesis Insuline stimulates intestinal cells multiplication in crypts

  19. Butyrate anti lipid metabolism Muscle percentage Vastus laterali muscle • Increase muscle in mice with hyperlipidic diet: Muscle protein quantification

  20. Encapsulated Calcium Butyrate Mode of Action • Biochimical and physiological effects • - Developement and protection of intestinal mucosa and villi (absoprtion, enzyme synthesis) • Energy for enterocytes (metabolism) • - Insuline production (villi, Ingestion) Microbiological effects - Normal microbism : positive development - Pathogen flora : Inhibition of : E. coli, Clostridium, Salmonella, Campylobacter…(Streptococcus S.) Semi therapeutical effects - Intestinale chronic inflammation (ref. Theory on GM – Niewold) - Immunity modulation: health vs growth (Saëman, Klaasing)

  21. INHIBITION OF COLIBACILLI BY VFA VFA concentration to reduce by 50% Colibacilli growth • Butyrate > Propionate > Acetate • pH reduction has a synergistic effect • Gàlfi and Neogràdy, 1992

  22. Effect on Clostridium: In Vivo Development of an in vivo model to study Clostridium perfringens infections (Timbermont, UG-VF 2007) • High protein diet (fishmeal), wheat-rye based • Inoculation of Eimeria vaccine (10x) (d19) • D18-D21: oral inoculation of Clostridium perfringens strain 56 (3x/day) • D22-D24: sampling for histology • Necrosis in > 50% of chickens • No mortality, semi quantitative scoring of gut damage Treatment of Clostridium perfringens infections in the in vivo model

  23. Susceptibility of 44 Clostridium strains (Butyrate) (2004) – pH = 6 Number of Strains with MIC ( mg/ml ) of : 4 8 16 Type Gen for Beta 2 toxin HORSE (11) 9 1 1 A 4 CATTLE (6) 2 4 A 1 CHICKEN (15) 13 2 A 3 RABBIT (12) 2 10 A 2 ALL 11 26 7 Prof. Dr. A. Decostere & Fr. Haesebrouck (Veterinary Faculty – UG –2004) – In press for publication – Veterinary Microbiology (2005)

  24. Effect of Butyrate on Clostridium and Chronic Enteritis 1) Direct inhibition at “intestinal” pH of ALL pathogenic strains from 5 animal species (broilers, pigs, rabbits, calves, horses) • Improving mucosa integrity offering less substrate (nutrients) to Clostridium perfringens (needs 13-14 Ess. AA’s). • Better digestion & absorption  less undigested nutrients 3) Anti inflammatory effect on G.I.T. (Enteritis = Inflammation) 4) Selective stimulation and inhibiton of various clusters of Clostridiaceae :  Inhibition of Cluster I (pathogenics)  Stimulation of Cluster IV and IVX (butyrogenic)

  25. Health effects of Calciumbutyrate Salmonella Genetics of Salmonella Picture of Salmonella

  26. Pathogenesis of Salmonella • Intestinal damage • Invasion in internal tissues • Excretion in environment

  27. GREENCAB 70 COATED and Salmonella control in broilers Salmonella invasion through epithelial cells at pH 7 and 6 with graded concentrations of GREENCAB 70 COATED (Van Immerseel 2004 - University Ghent – pH D Thesis) pH = 6 pH = 7 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0

  28. Encapsulated Ca-butyrate and Salmonella : 4-way action 1. Genetics : Downregulation of the expression of two genes (invasion and attachment) – Nutrigenomics 2. Intestinal lining : decrease invasion through epithelial cells (tight junctions) 3. Colonisation : decrease of growth in the different parts of the G.I.T. Inhibtion of Various Salmonella strains 4. Excretion : decrease of excretion (pig) and accumulation in cecum (poultry) – coated form only

  29. Encapsulated Calcium Butyrate Mode of Action • Biochimical and physiological effects • - Developement and protection of intestinal mucosa and villi (absoprtion, enzyme synthesis) • Energy for enterocytes (metabolism) • - Insuline production (villi, Ingestion) Microbiological effects - Normal microbism : positive development - Pathogen flora : Inhibition of : E. coli, Clostridium, Salmonella, Campylobacter…(Streptococcus S.) Semi therapeutical effects - Intestinale chronic inflammation (ref. Theory on GM – Niewold) - Immunity modulation: health vs growth (Saëman, Klaasing)

  30. Non-specific immunity modulation Prof. Kirk Klasing (California University Davis) : Bioactive Nutrients modulating immuneresponse (De Molenaar nr.8 12 april 2007) Non specific and inflammation Specific immunity Action of Butyrate E. Coli – Yolk sacinfection + : Vit E, PUFA Treg Coccidiosis + : Vit A - : PUFA B-cell Ig’s Intracellular pathogens

  31. Immune System D. Korver & M. Zuidhof (2007) Specific Immunity Innate (non specific) • Systemic changes in metabolism  systemic effect. • Energetically costly • Diverts nutrients from growth • Inflammation reaction • No memory (happens every time again) • Fever, Loss of appetite, Breakdown of muscle, Removal of nutrients from circulation, Acute phase proteins in the liver.. • Antibody (humoral) responses, • mediated by B cells • Directed (cell-mediated) cytotoxicity, mediated by cytotoxic T cells • = very specific, targetted, • Nutrient requirements are low Adaptive Immunity • Poorly developed at hatch • Vaccination : prior exposure to antigen challenge • Has a memory

  32. GREENCAB 70 COATED RESULTS IN ANIMAL PRODUCTION

  33. Greencab 75 P versus ABGP - CONFIDENTIALExperimental Station of European Industrial Company • Large experiment set up by European Feedmill to evaluate two commercial alternatives (Provimi, Nutreco) versus Avilamycin (CTR+) • Calcium butyrate at 4 levels was taken as other positive control : 60, 180, 300 and 420 grams per ton. • Outcome : * All calciumbutyrate groups performed better than the two commercial products. * All calciumbutyrate groups gave similar performance as 10 ppm avilamycin and better litter scores. * The lower dosages, 60 and 180 grams gave the better economy : 1.1-1.2% lower cost per kg of meat produced. Feedcost (%) 100 98.9 98.8 99.8 99.6

  34. Dosage Trial with Greencab 70 coated in broilers Research Institute CLO-DVV Belgium (M. Lippens & G. Huyghebaert) Mortality : 8.8% 7.5% 20.5 20.3 1.263 1.288 60.7 60.3 1.763 1.753 94.7 94.5 2.018 2.003 56.8 56.5 1.767 1.762 293 296 Lay out : 2 treatments x 5 replicates x 30-32 birds per pen - 0-42 days

  35. Trial with Greencab and Ovocrack in broilers Experimental Farm of European Feed Producer - 2003 0-11 days • Experiment station of European Feed mill. • Floor pen trial : 5 Treatments with 9 replicated and 80 birds per pen. Day 0-39 • Groups : CTR- : blanc control diet CTR+ : 10 ppm avilamycin 300 grams per ton Greencab 500 grams per ton Ovocrack (internal group by the feed mill, not shown) • Outcome : * All treatments performed better than the negative control. * Greencab and Ovocrack performed equal (better) than avilamycin * Ovocrack performs better than Greencab Side remark : Effects of treatments were higher in starter phase than in grower-finisher, most probably because of presence of an ionophore coccidiostat that may take over the role of ABGP in hygienic (trial station) conditions. 0-39 days FCR corrected for LWG

  36. GREENCAB 70 COATED BROILER 9 countries, 26 trials on average 7900 broilers per treatment, 0-39 days period • Daily weight gain • Feed conversion ratio • Mortality -1.2% • Litter moisture Improvement : Dosage recommendation : * : in difficult sanitary conditions or for salmonella control

  37. GREENCAB 70 COATED ECONOMICAL IMPACT

  38. GREENCAB 70 COATED IMPACT OF TECHNICAL PARAMETERS Economical impact for 50 000 broilers Economical impact per ton of feed

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