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  • 1

  • 2

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 3

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 4

    FACTORS INFLUENCING DISEASES IN ANIMALS AND CONSUMERS

    PROBLEMS MAY OCCUR FROM START TO FINISH

    GENETICS OF THE ANIMALCONTAMINATED RAW MATERIAL IN FEEDCONTAMINATION IN FEED PROCESSINGTRANSPORT AND STORAGE ON FARMNUTRITIONAL DEFICIENCIES OF FEEDMICROBIAL IMBALANCES IN THE ANIMALUNHYGIENIC FARM MANAGEMENTUNHYGIENIC SLAUGHTERHOUSE CONDITIONSTRANSPORT AND STORAGE AT THE DISTRIBUTORSTORAGE AND PROCESSING OF FOOD AT THE END-USER

    PATHOGENS

  • THE FOOD CHAIN5

  • 6

    RAW MATERIALS

    TRANSPORT

    FEED COMPOUNDING

    STORAGE AT MILL

    TRANSPORT

    STORAGE AT FARM

    DISTRIBUTION ON FARM

    CONSUMPTION BY ANIMAL

    ANIMAL PERFORMANCE

    ANIMAL

    TRANSPORT

    SLAUGHTER

    MEAT

    PACKAGING

    STORAGE

    TRANSPORT

    RETAIL

    STORAGE

    CONSUMPTION

    FACTORS INFLUENCING DISEASE IN ANIMALS

    AND CONSUMERS

    MAIN FOCUS IS THE HEALTH OF THE ANIMALS ON FARM

  • 7

    THE EVOLUTIONOF DISEASES

  • 8

    0%

    10%

    20%

    30%

    40%

    50%

    60%

    70%

    80%

    90%

    100%

    1880 1997

    OTHER DISEASES

    INFECTIOUS AND PARASITIC DISEASES

    DISEASES OF THE RESPIRATORY SYSTEM

    DISEASES OF THE CIRCULATORY SYSTEM

    NEOPLASM (CANCERS)

    CAUSES OF DEATH IN ENGLAND AND WALES: 1880 AND 1997

    THE EVOLUTION OF DISEASES

  • 9

    RISK FACTORS

    SANITARY CONDITIONS

    LITTER QUALITY TURNOVER TIME

    DRINKING MANAGEMENT CLEANINGFACILITIES BACTERIAL CONTAMINATION

    GENETICS

    BREEDING

    VACCINE CHALLENGE

    DENSITY STRESS POOR IMMUNITY

    DIETARY CHANGE

    SEASON

    NUTRITION

    HIGH NUTRIENTDENSITY DIETS

    DIGESTIBILITY PARTICLE SIZE

    TYPE OF CEREALS

    TOXINS

    MICROBIALIMBALANCE

    9

  • 10

    THE KEY OBJECTIVES IN ANIMAL HUSBANDRY

    OPTIMISE THE EFFICIENCY OF FOOD PRODUCTION

    PREVENT DISEASES

    ANTIBIOTICS WERE USED INPREVENTION AND IN THERAPY

    BUT………

  • 1111

  • 12

    FEED ADDITIVES

    1970 2006 2008 2012

    ADDITIVES AUTHORISED

    ANTIBIOTICGROWTH PROMOTERSBANNED

    INCREASED USE OF VETERINARY MEDICINAL ANTIBIOTICS

    COCCIDIOSTATSAND HISTOMONOSTATSTO BE BANNED?

    VMP ONLYNUTRITIONALADDITIVESCHANGE FROMFEEDSTUFFS REGULATIONTO FEED ADDITIVES E.G. AMINO ACIDS

  • 13

    20.5

    21

    21.5

    22

    22.5

    23

    23.5

    1150

    1200

    1250

    1300

    1350

    1400

    1999 2000 2001 2002 2003 2004 2005 2006 2007

    BAN

    USE OF ANITBIOTICS IN FRANCE (TONS)FEED PRODUCTION (MILLION TONS)

    SOURCE: AGENCE FRANÇAISE DE SECURITE SANITAIRE DES ALIMENTS – AFSSA + FEFAC

  • 14

    USE OF ANTIBIOTICS IN FRANCE

    AMINOGLYCOSIDES ± 5%ß-LACTAMINES ± 8%CEPHALOSPORINES < 1%OTHERS < 2%FLUOROQUINOLONES < 1%FURANES < 1%MACROLIDES 7%PHENICOLES < 1%POLYPEPTIDES 5%QUINOLONES < 2%SULPHONAMIDES ± 16%TETRACYCLINES ± 50%TRIMETHOPRIMES < 3%

    SOURCE: AGENCE FRANÇAISE DE SECURITE SANITAIRE DES ALIMENTS – AFSSA

  • 15

    1930 1940 1950 1960 1970 1980 1990 2000

    SULPHONAMIDES 1935 - 1950

    PENICILLIN 1942 - 1946

    STREPTOMYCINE 1943 - 1957

    CHLORAMPHENICOL 1946 - 1957

    TETRACYCLINE 1948 - 1953

    ERYTHROMYCINE 1952 - 1988

    VANCOMYCINE 1957 - 1987

    METICILLIN 1960 - 1962

    AMPICILLIN 1963 - 1973

    CEPHALOSPORINES 1961 - 1969

    LINEZOID 2000 - 2002

    DAPTOMYCINE 2003 - 2005

    TIME BETWEEN 1ST MARKETING AND 1ST RESISTANCE

    SOURCE: SCIENCE & VIE

  • 16

    BALANCED HEALTHY ANIMAL/ HUMAN BEING

    IMBALANCED UNHEALTHY ANIMAL/ HUMAN BEING

    PATHOGENS

    TREATMENT

    PATHOGENS

    THERAPEUTIC TREATMENTTREATED

    BALANCED HEALTHY ANIMAL/ HUMAN BEING

    GENERAL PERCEPTION: WHEN ILL TAKE MEDICINE

  • 1717

    BALANCED HEALTHY ANIMAL/ HUMAN BEING

    PREVENTIVETREATMENT

    (BALANCED) HEALTHY ANIMAL/ HUMAN BEING

    PREVENTIVETREATMENT

    PATHOGENS

    BALANCED HEALTHY ANIMAL/ HUMAN BEING

    PREVENTIVE TREATMENT

    PREVENTIVETREATMENT

    PATHOGENS

    PREVENTIVE TREATMENT NOT WORKINGGENERAL PERCEPTION: WHEN NOT ILL PREVENTION IS ONLY A FEEBLE INSURRANCE POLICY

  • 18

    SO WHO OR WHAT ARETHOSE PATHOGENS

    AND WHERE DO THEY COME FROM?

  • 19

    STROMATOLITES OF FOSSILIZED OXYGEN-PRODUCING CYANOBACTERIA HAVE BEEN FOUND FROM 2.8 BILLION YEARS AGO, POSSIBLY AS OLD AS 3.5 BILLION YEARS AGO.

    Pre-Cambrian stromatolites in the Glacier National Park, Montana

    THE OLDEST ORGANISMS ON EARTH

    http://upload.wikimedia.org/wikipedia/commons/c/c0/Stromatolites.jpghttp://upload.wikimedia.org/wikipedia/commons/c/c0/Stromatolites.jpg

  • 20

    COST VERSUS EFFICACY

    PARAMETERS TO CONSIDER

    COST OF RAW MATERIALSCOST OF PRODUCTIONCOST OF DISTRIBUTION

    IMPROVEMENTOBTAINED IN

    VALUE

    PERCEIVED OR ACTUAL

  • 21

    PRODUCTS IN PREVENTING DISEASEIN ANIMAL HUSBANDRY

    ORGANIC ACIDS

    PREBIOTICSOLIGOSACCHARIDES

    PROBIOTICSYEASTSBACTERIA

    PHYTO-THERAPEUTICSPLANT EXTRACTSESSENTIAL OILS

    NUCLEOTIDES

    NUTRIGENOMICS

    THE TENDENCY IN EUROPE IS TO REPLACE ANTIBIOTIC GROWTHPROMOTERS BY A WHOLE RANGE OF PRODUCTS.

  • 22

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 23

    ORGANIC ACIDS

    ORGANIC ACIDS ARE USED SINCE THE EARLY DAYS OF INTENSIVE ANIMAL HUSBANDRY

    SOME OF THE KEY ACIDS ARE:ACETICBENZOICFORMICFUMARICLACTICPROPIONIC

    COMBINATIONS OF THE ABOVE AND THEIR RESPECTIVE SALTS

    LET’S HAVE A LOOK AT SOME OF THE HISTORY

  • 24

    ACCORDING TO SHENNONG’S HERB CLASSIC, VINEGAR WAS INVENTED IN CHINA DURING THE XIA DYNASTY, AROUND 2000 BC.

    SHENNONG TASTING HERBS TO DISCOVER THEIR QUALITIES

    IN THE 8TH CENTURY THE MUSLIM ALCHEMIST JABIR IBN HAYYAN (GEBER) WAS THE FIRST TO CONCENTRATE ACETIC ACID FROM VINEGAR THROUGH DISTILLATION.

    15TH-CENTURY EUROPEAN PORTRAIT OF "GEBER", CODICI ASHBURNHAMIANI1166, BIBLIOTECA MEDICEA LAURENZIANA, FLORENCE

    HISTORY

    http://upload.wikimedia.org/wikipedia/commons/c/c5/Shennong3.jpghttp://en.wikipedia.org/wiki/Shennonghttp://en.wikipedia.org/wiki/File:Jabir_ibn_Hayyan.jpg

  • 25

    HISTORY

  • 26

    HISTORY

  • 27

    BENZOIC ACID WAS DISCOVERED IN THE 16TH CENTURY. THE DRY DISTILLATION OF GUM BENZOIN FIRST DESCRIBED BY NOSTRADAMUS (1556).

    GUM BENZOIN IS A BASLAMIC RESIN DERVIED FROM THE BARK OF DIFFERENT TREES OF THE GENUS STYRAX.

    MICHEL DE NOSTREDAME

    NOSTRADAMUS: ORIGINAL PORTRAIT BY HIS SON CESAR

    (STYRAX BENZOIN) PARTS DRAWING.FRANZ EUGEN KÖHLER:

    KÖHLER'S MEDIZINAL-PFLANZENIN NATURGETREUEN ABBILDUNGEN, ETC. (1887)

    HISTORY

    http://en.wikipedia.org/wiki/File:Koeh-133.jpghttp://en.wikipedia.org/wiki/Styrax_benzoinhttp://en.wikipedia.org/wiki/Styrax_benzoinhttp://en.wikipedia.org/wiki/Styrax_benzoinhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/Franz_Eugen_K%C3%B6hlerhttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plantshttp://en.wikipedia.org/wiki/K%C3%B6hler's_Medicinal_Plants

  • 28

    ORGANIC ACIDS

    ORGANIC ACIDS ARE PRIMARILY USED IN PIG DIETS, WHEREBY THE ACIDS LOWER THE pH OF THE GUT, HENCE CREATING AN ENVIRONMENT WHICH DISCOURAGES THE GROWTH OFPATHOGENS

    KEY ISSUES THE COMPANIES SELLING THESE PRODUCTS (SINGLE ORCOMBINED) HAVE AUTHORISED THESE AS TECHNOLOGICALFEED ADDITIVES WHILST THEIR MARKTING IS TO PROMOTETHEM AS ZOOTECHNICAL FEED ADDITIVES

    THIS YEAR ALL DOSSIERS FOR ORGANIC ACIDS AS PRESERVATIVESWILL BE SUBMITTED TO EFSA BEFORE 8 NOVEMBER

  • 29

    LND: LOWER NUTRIENT DENSITY

    BROILER TRIAL CONDUCTED IN TURKEYSPONSOR: BIOMIN

    RESULTS IN THE FIELD

    PIG TRIAL CONDUCTED IN ROMANIASPONSOR: BIOMIN

  • 30

    0

    50

    100

    150

    200

    250

    2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

    EUROPE

    WORLDWIDE

    FORMIC ACID SALES IN ANIMAL HUSBANDRY($ MILLIONS)

    USE OF FORMIC ACID IN ANIMAL HUSBANDRY

    APPROX. 40 000 TONS IN 2010

  • 31

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • PREBIOTICS AND PROBIOTICS

    32

    PREBIOTICS

    PROBIOTICS

    VIABLE VBNC* INACTIVATED COMPETITIVECELLS CELLS ** EXCLUSION

    *VBNC = VIABLE BUT NON-CULTURABLE; ** CONSIDERED AS A RAW MATERIAL IN THE EU

    OLIGOSACCHARIDES (FOS, MOS)

  • 33

    PREBIOTICS AND PROBIOTICS

    PRE- AND PROBIOTICS ARE USEDIN ALL ANIMAL DIETS, MAINTAINING AN IMPROVED GUT MICROFLORA ANDCONSEQUENTLY BETTER GROWTH PERFORMANCES

    KEY ISSUES IN THE 90 ‘S NUMEROUS PROBIOTICS WEREINTRODUCED IN A ME-TOO FASHION, CREATING A NEGATIVE IMAGE

    IN THE LAST DECADE MORE SCIENTIFIC WORK WAS CONDUCTED .THE WORLDWIDE MARKET INCLUDING PRE- /PROBIOTICS + YEAST CELL WALLS (FEED INGREDIENT ACCORDING TO 767/2009)IS NOW OF THE ORDER OF WELL OVER US$ 1.5 BILLION

  • 34

    MARCEL ROBERFROID IN 1995

    STUDIES HAVE DEMONSTRATED POSITIVE EFFECTS ON CALCIUM AND OTHER MINERAL ABSORPTION, IMMUNE SYSTEM EFFECTIVENESS, BOWEL pH, REDUCTION OF COLORECTAL CANCER RISK, INFLAMMATORY BOWEL DISORDERS (CROHN'S DISEASE AND ULCERATIVE COLITIS) HYPERTENSION (HIGH BLOOD PRESSURE) AND INTESTINAL REGULARITY.

    PREBIOTICS

  • 35

    MODE OF ACTION OF OLIGOSACCHARIDES

  • 36

    PROBIOTICS

    HISTORYELIE METCHNIKOFF, NOBEL PRIZE WINNER IN 1908 WAS THE FIRST PERSON TO INTRODUCE THE CONCEPT OF REPLACING HARMFUL BACTERIA BY USEFUL ONES

    IN THE INTESTINE

    MOREOVER HE PROPOSED THE CONSUMPTIONOF FERMENTED MILK CONTAINING LACTIC ACIDBACTERIA AND LOWERING THE INTESTINAL pH.

  • 37

  • QPS granted micro-organisms

    Bifidobacterium adolescentisBifidobacterium animalisBifidobacterium bifidumBifidobacterium breveBifidobacterium longum

    Lactobacillus acidophilusLactobacillus amylolyticusLactobacillus amylovorusLactobacillus alimentariusLactobacillus aviariesLactobacillus brevisLactobacillus buchneriLactobacillus casei **Lactobacillus coryniformisLactobacillus crispatusLactobacillus curvatusLactobacillus delbrueckiiLactobacillus farciminisLactobacillus fermentumLactobacillus gallinarumLactobacillus gasseriLactobacillus helveticusLactobacillus hilgardiiLactobacillus johnsoniiLactobacillus kefiranofaciensLactobacillus kefiriLactobacillus mucosaeLactobacillus panisLactobacillus paracaseiLactobacillus paraplantarumLactobacillus pentosusLactobacillus plantarumLactobacillus pontisLactobacillus reuteriLactobacillus rhamnosusLactobacillus sakeiLactobacillus salivariusLactobacillus sanfranciscensis

    Lactococcus lactis

    Leuconostoc citreumLeuconostoc lactis Leuconostoc mesenteroides

    Pediococcus acidilacticiPediococcus dextrinicusPediococcus pentosaceus

    Propionibacterium. Freudenreichii

    Streptococcus Thermophilus

    Bacillus amyloliquefaciensBacillus atrophaeusBacillus clausiiBacillus coagulansBacillus fusiformisBacillus lentusBacillus licheniformisBacillus megateriumBacillus mojavensisBacillus pumilusBacillus subtilisBacillus vallismortisGeobacillus stearothermophillus

    Debaryomyces hanseniiHanseniaspora uvarumKluyveromyces lactis Kluyveromyces marxianusPichia angustaPichia anomala Pichia jadinii.Saccharomyces bayanusSaccharomyces cerevisiae Saccharomyces pastorianus(synonym of Saccharomycescarlsbergensis)

    38QPS: Qualified Presumption of safety

  • 39

    MODE OF ACTIONOF PROBIOTICS

    NUTRITIONAL EFFECT

    REDUCTION OF METABOLIC REACTIONS THAT PRODUCES TOXIC SUBSTANCESSTIMULATION OF INDIGENOUS ENZYMESPRODUCTION OF VITAMINS OR ANTIMICROBIAL SUBSTANCES

    SANITARY EFFECT

    INCREASE IN COLONISATION RESISTANCESTIMULATION OF THE IMMUNE SYSTEM

  • 40

    VIABLE BUT NON CULTURABLE BACTERIAMODE OF ACTION OF SORBIFLORE®

    Metabolites produced byLactobacillus farciminis

    andLactobacillus rhamnosus

    Bacteriocin-likesubstances

    Polysaccharides

    Organic acids(Lactic & Acetic acid)

    Hydrogen peroxide

    Bacterial cellwalls

    EnzymesLipolytic, esterolytic

    amylolytic, andcellulolytic

    Amino acidsand

    vitamins

    Anti-microbial activity Nutritional Immune stimulation

  • 41

    LACTOBACILLUS RHAMNOSUS ADHERES TO THE GUT WALL, HENCE PROVIDING A BARRIER

    41

  • 42

    21.4

    21.6

    21.8

    22

    22.2

    22.4

    22.6

    22.8

    23

    23.2

    23.4

    42 days

    Control

    Treated

    365

    370

    375

    380

    385

    390

    395

    400

    405

    410

    415

    42 days

    Control

    Treated

    RESULTS IN PIGLETS

    BODY WEIGHT (KG)

    ADG (G)

  • 43

    2950

    3000

    3050

    3100

    3150

    3200

    3250

    3300

    3350

    3400

    3450

    3500

    49 days

    Control

    Treatment

    BODY WEIGHT (KG)

    27000 BROILERS PER TREATMENT49 DAYS

  • CELLS CONTACT BETWEEN LACTOBACILLI AND SPIROCHAETES

    44

  • 45

    BRACHYSPIRA AND ITS EFFECT IN ANIMAL HUSBANDRY

    BRACHYSPIRAAND EGG DROP SYNDROME

    BRACHYSPIRA

    BRACHYSPIRAAND DIARRHOEA IN PIGS

  • 46

    SACCHAROMYCES CEREVISIAE

  • 47

    RESULTS IN PIGLETSBODY WEIGHT (KG)

    ADG AND FCR WERE ALSO SIGNIFICANTLY DIFFERENT

    TRIAL WITH SACCHAROMYCES CEREVISAE

    0

    5

    10

    15

    20

    25

    DAY 0 DAY 42

    CONTROL

    TREATMENT

  • 4848

    COMPETITIVE EXCLUSION

    GEORGII FRANTSEVICH GAUSE

    IN 1932, GAUSE PUBLISHED WHAT HAS BECOME KNOWN AS THE COMPETITIVE EXCLUSION PRINCIPLE

    TWO SPECIES COMPETING FOR THE SAME RESOURCES CANNOT STABLY COEXIST

  • 49

    COMPETITIVE EXCLUSION

  • 50

    COMPETITIVE EXCLUSION

  • ANIMAL SPECIES PRODUCT DESCRIPTION USAGE/CLAIM TYPE

    ACC TO EU

    BEEF CATTLE Bovamine Lactobacillusacidophilus

    Reduces Escherichia coli O157:H7

    Probiotic

    Probiotic

    DAIRY CATTLE LiveBac Dried extract from yeast and bacterial fermentation

    Reduces acidosis Probiotic

    Raw material

    LactoEdge L. acidophilus, Saccharomyces cerevisiae,MOS

    Prevention of scours in calves

    Competitive exclusion; probiotic; prebiotic

    Probiotic + prebiotic

    PRODUCTS ON THE USA MARKET

  • 52

    ANIMAL SPECIES PRODUCT DESCRIPTION USAGE/CLAIM TYPE

    ACC TO EU

    POULTRY Aviguard Freeze-dried product from healthy pathogen-free chickens

    Protection against E. coli, Salmonella, Clostridia

    Competitive exclusion

    Competitive exclusion

    Fastrack S. cerevisiae, Enterococcus faecium, L. acidophilus, amylase from Bacillus subtilis and Aspergillus oryzae, protease from B. subtilis, FOS

    Performance and immune stimulation

    Probiotic

    Probiotic, zootechnical additives (enzymes) + prebiotic

    PRODUCTS ON THE USA MARKET

  • 53

    ANIMAL SPECIES PRODUCT DESCRIPTION USAGE/CLAIM TYPE

    ACC TO EU

    PIG Biofeed Mixed bacteria and antibodies

    Reduction of diarrhoea

    Probiotic

    Not accepted

    Premidex Modified starch Improved performance and decreased pathogen colonisation

    Prebiotic

    If no GMO -> raw materialIf GMO possibly a zootechnical additive

    PRODUCTS ON THE USA MARKET

  • 54

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 55

    ESSENTIAL OILS AND PLANT EXTRACTS

    PHYTO THERAPEUTICS HAVE BEEN USED FOR CENTURIES PRIMARILY IN HUMAN MEDICINE

    IN THE EU THEY FALL UNDER THE CATEGORY OF “SENSORY ADDITIVES”

    SINCE THE BEGINNING OF THIS CENTURY THEY BECAMEMORE COMMON IN ANIMAL HUSBANDRY

    SOME ISSUES ARE: • THE EU LEGISLATION• ITS MODE OF ACTION• A LOT OF ME-TOO PRODUCERS

  • 56

    THE HISTORY OF PLANT EXTRACTS

    GINGER EXTRACTS WERE USED TO ALLEVIATE ALIMENTARY TRACT PROBLEMSTHE BRITISH PHARMACOPOEIA IN 1885 CONTAINED MORE PLANT DERIVED PRODUCTSTHAN CHEMICALLY SYNTHESIZED

  • 57

    THE ASSYRIANS IN 8TH CENTURY BC USED A MIXTURE OF BELLADONNA,CANNABIS AND MANDRAKE ROOT (NIGHTSHADES – SOLANACEAE)AS PAINKILLER

    THE HISTORY OF PLANT EXTRACTS

    http://upload.wikimedia.org/wikipedia/commons/7/79/Cannabis_sativa_Koehler_drawing.jpghttp://en.wikipedia.org/wiki/File:Mandrake-roots.jpghttp://upload.wikimedia.org/wikipedia/commons/2/2b/Koeh-018.jpg

  • 58

    THE VEDIC TEXTS (VEDAS IN SANSKRIT = KNOWLEDGE) DATED 2ND – 1ST MILLENIUM BCLISTS 700 SUBSTANCES INCLUDINGCINNAMON, GINGER, CORIANDER, ETC.ALL THESE PRODUCTS ARE NOW USED INPHYTO-THERAPEUTICS

    THE HISTORY OF PLANT EXTRACTS

    http://upload.wikimedia.org/wikipedia/commons/e/ed/Koeh-193.jpghttp://upload.wikimedia.org/wikipedia/commons/e/e1/Cinnamomum_verum1.jpg

  • 59

    THE EU LEGISLATION

    THEY ARE CLASSIFIED AS “SENSORY” ADDITIVES

    NO CLAIM TO GROWTH PERFORMANCE

    THE COMPLEX NATURE OF ONE OR MOREACTIVE INGREDIENTS

    MAKES IT DIFFICULT TO PRODUCE A DOSSIERFOR A ZOOTECHNICAL ADDITIVE, ESPECIALLY THE PART CONCERNING SAFETY

    EXAMPLE ON SUBSEQUENT SLIDES

  • Choleretic effect (increases biliary secretion and lipids release).

    Foie

    Artichoke Cynarin Boldo

    Diuretic, choleretic and antioxidant effect

    Boldin

    RosemaryRosmarinic acid

    Milk thistle

    Silymarin (silybin)

    Lipotropic effect and cellular protection of hepatocyt

    Detoxifying (increases Glutathion-S-transferase activity)

    PLANT EXTRACTS HAVING AN EFFECT UPONLIVER METABOLISM IN DAIRY

    60

  • 61

    Artichoke

    Cynarin

    HPLC chromatogram

    of the determination of the cynarin

    content

    Active component:

    COMPONENTS OF THE PRODUCT

  • Rosemary

    Active component: HPLC chromatogram

    of the determination of the

    rosmarinic acid content

    COMPONENTS OF THE PRODUCT

    62

  • 63

    milk thistle

    Silymarin (a blend of 3 isomers)

    and derivatives

    Active component:

    HPLC chromatogram

    of the determination of the

    silymarin content

    COMPONENTS OF THE PRODUCT

  • Boldo

    Boldine

    Active component:

    HPLC chromatogram

    of the determination of the boldine

    content

    COMPONENTS OF THE PRODUCT

    64

  • 65

    MEASURABLE RESULTS

    IMPROVEMENT OF LIVER FUNCTIONS

    REDUCTION OF SANITARY PROBLEMS AND INFERTILITY

    Frequency of sanitary troubles

    specific to steatosis

    35.3%

    17.1%

    0%

    10%

    20%

    30%

    40%

    interval calving- fertilizing insemination

    122

    106

    95

    100

    105

    110

    115

    120

    125Reduction

    by 50%

    2 weeks improvement

    Reduction of NEFA ( *) for cows

    with high steatosis

    -0.32

    -0.48

    -0.7-0.6-0.5-0.4

    -0.3-0.2-0.10.0

    Reduction of ketones ( **) for

    cows with high steatosis

    -0.25

    -0.66-0.7-0.6-0.5-0.4-0.3-0.2-0.10.0

    mmol / lmmol / l

    Reduction of biliary acids for cows

    with high steatosis

    15.42

    -26.30-30

    -20

    -10

    0

    10

    20

    µ mol / l

    (*) : NEFA = Non Esterified Fatty Acids, one of the main parameters of steatosis.

    (**) : Ketonic bodies are produced by free fatty acids . B OHC4 (beta hydroxy butyrate) is measured.

    Results obtained by animals with high steatosis.

    Control

    Treated

    days

  • PLANT EXTRACTS HAVING AN EFFECT UPONNECROTIC ENTERITIS IN BROILERS

    MODE OF ACTION

    INCREASED PERMEABILITY OF THE MEMBRANE

    MODIFICATION OF THE ENZYMATIC ACTIVITY

    EFFECT UPON MITCHONDRIA

    66

  • ELECTRON MICROSCOPY REVEALS THAT THE MEMBRANE IS ATTACKED

    C. albicans treated with 800 g/ml of cinnamaldehyde

    Candida albicans (control)

    C. albicans treated with 600 g/ml of cinnamaldehyde

    GAP FORMATION AND STRUCTURAL MODIFICATION OF CELL WALL

    CANDIDA ALBICANS WITH SEM*: EXTERNAL OBSERVATIONS

    INCREASED PERMEABILITY OF THE MEMBRANE

    SEM: SCANNING ELECTRON MICROSCOPY 67

  • SEPARATION OF PLASMA MEMBRANE

    reservesNucleus

    Cell wall

    C. ALBICANS TREATED WITH 500 G/ML OF CINNAMALDEHYDE

    CONTROL

    CANDIDA ALBICANS WITH TEM*: INTERNAL OBSERVATIONS

    INCREASED PERMEABILITY OF THE MEMBRANE

    TEM: TRANSMISSION ELECTRON MICROSCOPY 68

  • DRASTIC INHIBITION OF ENZYMATIC ACTIVITIES

    BIOCHEMICAL MODIFICATIONS

    MODIFICATION OF ENZYMATIC PROFILE

    MODIFICATION OF THE ENZYMATIC ACTIVITY

    69

  • EFFECT OF CNMA ON THE MEMBRANE POTENTIAL OF B. CEREUSWITH GLUCOSE (GLU), NIGERICIN (NIG).

    PERMEABILITY OF MEMBRANE IS AFFECTED WITH INCREASED LEVELS OF CNMA

    MODIFICATION OF THE ENZYMATIC ACTIVITY

    BIOCHEMICAL MODIFICATIONS

    MODIFICATION MEMBRANE PERMEABILITY

    70

    CNMA: CINNAMALDEHYDE

  • MODIFICATION OF GLUCOSE PERMEABILITY

    DECREASE OF ATP SYNTHESIS IN MITOCHONDRIA

    ADP

    ATP

    EFFECTS OF AEN ON PLASMA MEMBRANE

    EFFECT UPON MITOCHONDRIA

    71

  • 72

    OVERALL RESULTS

    EuronutritionFrance – 2002Trial AEN 700 at 500 g/Tonne

    RESULTS

    1580

    1590

    1600

    1610

    1620

    1630

    1640

    1650

    1660

    1670

    1680

    Control AEN 350

    Weight

    1.78

    1.8

    1.82

    1.84

    1.86

    1.88

    1.9

    1.92

    1.94

    Control AEN 350

    Feed conversion

  • 73

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 74

    NUCLEOTIDESNUCLEOTIDES ARE USED IN SOME PIG, HORSE DIETS, BUT PRIMARILY IN FISH.SOME WORK SHOWS PROLONGATION OF THE VILLIHENCE INDIRECT STIMULATION OF THE IMMUNE-SYSTEM

    KEY ISSUES EXPENSIVE AND THE RESULTS ARE NOT ALWAYS OBVIOUS

    URIDINE

  • 75

    THE USE OF NUCLEOTIDES IN FEED CAN RESULT IN SIGNIFICANT DIFFERENCES IN VILLILENGTH WITH 28 DAY OLD PIGLETS.

    Xavier Córdoba, Elisabet Borda, Daniel Martínez-Puig and GerardHinojo, Bioiberica, Spain

    THE EFFECT OF NUCLEOTIDES UPON PIGLETS

  • 76

    THE EFFECT OF NUCLEOTIDES UPON PIGLETS

  • 77

    THE EFFECT OF NUCLEOTIDES UPON PIGLETS

    Providing a nucleotide-enriched prestarter diet to piglets aged between 21 and 35 days,produced animals in which productive effects could be observed in the starter diet period of35-56 days of age, when the diet no longer contained nucleotides.Nucleotides improve the production parameters of animals by enhancing the development ofthe immune system and the intestinal mucosa of piglets, reducing the stress and delays thatthe animals may suffer as a result of various diseases or post-weaning stress. Furthermore, theeffect of nucleotides is long-lasting, in that they develop important tissues such as those of theimmune system and the intestinal mucosa.

  • 78

    THE EFFECT OF NUCLEOTIDES UPON FISH

    VANNAGEN ENHANCES THE PERFORMANCE OF ASIAN SEA BASS

    UNIT CONTROL TREATMENT CONTROL = 100%

    INITIAL WEIGHT g 34.4 34.4

    FINAL WEIGHT g 252.1 275.7

    WEIGHT GAIN g 217.8 241.3 110.8

    DAILY WEIGHT GAIN g 2.27 2.51 110.7

    FCR 2.60 2.01 77.3

    TRIAL PERIOD 96 DAYS

  • 79

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • NUTRIGENOMICS

    • Study of molecular

    relationships between genes

    • Responses to specific biologically active nutrients

    • Relationships that impact animal health and performance

    80

  • MICROARRAY TECHNOLOGY

    • Discovered nutrients & compounds can “turn on” or “turn off” genes & gene expression

    • Gene regulation impacts health of the animal

    81

  • Healthy Immune System

    • Benefits

    – Reduced mastitis

    – Reduced metritis

    – Lower somatic cell counts

    – Less death loss

    – Fewer culls

    – Better reproduction efficiency

    – Increased milk production

    82

  • Mode of Action

    • OmniGen-AF is a proprietary formulation of specific biologically active nutrients that modulate the genetic expression of genes responsible for cellular health

    • Normalize innate immune function– Increased neutrophil migration to infection site– Improved neutrophil killing capabilities

    • Adaptive immune system modulation is under investigation

    • Improved immune function can reduce disease & improve performance– Less mastitis – More milk

    production– Reduced SCC – Better

    reproduction– Less metritis– Lower death lose

    83

  • Powerful medicineThe Immune System

    • It’s more cost effective to prevent disease than to treat it.

    • The most powerful medicine is the cows own immune system

    • Immune system has two parts

    – Adaptive Immunity

    – Innate Immunity (OmniGen-AF)

    84

  • Adaptive Immunity

    – Very specific

    – Long lasting

    – Days or weeks to develop

    85

  • Innate Immune System

    • Immediate response to invading organisms and infections

    • Non-specific

    – Bacteria

    – Viruses

    – Molds

    – parasites

    86

  • Multi-Layered Protection• Skin• Epithelial linings

    in gut and lungs• GI tract acids

    and enzymes• Blood components

    (white blood cells)– Neutrophils– Macrophagess– Dendritic cells

    • Identify and kill pathogens until adaptive immune system is established

    87

  • Role of Macrophages • Monitor for all

    invading pathogens

    • Inhabit the alveolus in mammary gland

    • Detection releases cytokines and chemokines into capillaries

    • Signal Neutrophils moving through capillaries to stop and migrate to area

    88

  • Role of Neutrophils

    • Neutrophils detect chemical and hormonal signals from Macrophages

    • Neutrophils tether to the capillary wall using L-selectin

    • They squeeze through capillary wall and enter mammary gland to find pathogens

    89

  • Phagocytosis

    • Neutrophils

    – identify pathogens

    – engulf them

    – destroy them with enzymes or reactive oxygen species (ROS)

    90

  • 91

    Summary

    • OmniGen-AF is a proprietary blend of biologically active nutrients that support the innate immune system

    • Prince has conducted approximately 170 trials demonstrating mode of action and benefits of feeding OmniGen-AF

    • The benefits of a properly functioning immune system are numerous

    – Reduced mastitis– Reduced metritis– Lower somatic cell counts– Less death loss– Fewer culls– Better reproduction efficiency– Increased milk production

  • 92

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 93

    QUORUM SENSING

    9393

    N-ACETYL HOMOSERINE LACTONE (AHL)

    ACTIVATION TRANSCRIPTIONOF CERTAIN GENES

    INDUCTION SYNTHESIS

    FORMATION OF BIOFILM DISEASE

  • 94

    QUORUM SENSING

  • 9595

    QUORUM SENSING

    N-ACETYL HOMOSERINE LACTONE (AHL)

    ACTIVATION TRANSCRIPTIONOF CERTAIN GENES

    INDUCTION SYNTHESIS

    FORMATION OF BIOFILM DISEASE

    QUORUM QUENCHING

  • 96

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 9797

    LACTOCEUTICALSLACTOFERRIN AND LACTOPEROXIDASE ARE POTENT ANTIMICROBIAL AGENTS AND FOUND IN HUMANSIN MANY DIFFERENT BODY FLUIDS

    LACTOFERRIN

    USED IN ASIA IN INFANTMILK, IN COSMETICS,AS PRESERVATIVE ANDANTIOXIDANT

    http://upload.wikimedia.org/wikipedia/commons/1/1f/Lactoferrin.png

  • 98LACTOPEROXIDASE

    LACTOCEUTICALS

    H2O2 + SCN- OSCN- + H2O

    PEROXIDE + THIOCYANATE HYPOCYANITE

    LACTOPEROXIDASE

    POWERFUL ANITMICROBIAL ACTION

    USED TO PRESERVEFOODS, INCL. MEATMILK, VEGETABLES,ETC.

    http://upload.wikimedia.org/wikipedia/commons/a/a2/Lactoperoxidase.png

  • 99

    COULD THESE MOLECULES BE POTENTIALLY USED IN ANIMAL HUSBANDRY?

    ONE OF THE LEADING DAIRY COMPANIES IN JAPAN, MORINAGA LOOKED AT THE POSSIBILITY TO USE THESE MOLECULES IN ANIMAL HUSBANDRY INTHE MID 90’S.

    AT THE TIME THE MANUFACTURING COST WAS TOO HIGH

    PRESENTLY LACTOFERRIN IS PRODUCED IN SEVERAL WAYS

    hrLACTOFERRIN VIA TRANSGENIC COWS IN THE USAbLACTOFERRIN FOR THE USE IN INFANT MILK

    hr: HUMAN RECOMBINANT; b: BOVINE

  • 100

    INTRODUCTION

    ORGANIC ACIDS

    PREBIOTICS AND PROBIOTICS

    PHYTO-THERAPEUTICS

    NUCLEOTIDES

    NUTRIGENOMICS

    QUORUM SENSING

    LACTOCEUTICALS

    AFTERTHOUGHTS

    THE PREVENTION OF DISEASES IN FARM ANIMALS

  • 101CYANOBACTERIA IN LAKE ATITLÁN, GUATEMALA

    THE OLDEST LIVING ORGANISM VERSUS THE YOUNGEST

    WE ARE FIGHTING THE OLDEST KNOWN ORGANISMSWITH TOOLS WE DEVELOPED IN THE LAST CENTURY ONLY

    THESE ORGANISMS HAVE BEEN ABLE TO ADAPTTO THE MOST PRECARIOUS CONDITIONS FOR OVER2 BILLIONS OF YEARS

    http://upload.wikimedia.org/wikipedia/commons/1/11/Harmful_Bloom_in_Lake_Atitl%C3%A1n,_Guatemala.jpg

  • 102

    THE FUTURE

    QUORUM QUENCHING

    GMO ANIMALS – DISEASE FREE

    GMO CROPS – USED AS PREVENTIVE MEDICATION

    NUTRIENTS ACTING UPON ATP-RECEPTORS

    LACTOCEUTICALS

    DESIGNER PREVENTIVE DRUGS

    NANOTECHNOLOGY

  • 103

    WHAT ARE THE HURDLES FORINNOVATION IN THE EU?

  • 104104

  • 105

    THE MAJORITYARE ME-TOO COPIERS

    THE REST SLEEPS

    ORIGINALITYAND SCIENTIFICALLY BASEDPRODUCERS

    HIGHLOW

    PRODUCERS

    FEW COMPANIESHAVE THE OVERALL

    SKILLS

  • 106

    THE ROAD OF DISCOVERIES IS LONG AND NEVER

    ENDING

    ALTHOUGH SOME DISEASES WILL BE A THING OF THE PASSED

    WE WILL ALWAYS HAVE TO FACE NEWCHALLENGES

  • 107