Calcium-butyrate SINTOBUTYL Product and specifications Calcium-butyrate : Product and specifications Sintobutyl - Chemically pure calciumbutyrate (slight surplus of Ca) – fine powder - Doesn’t smell if not touched with humid surfaces (hands, ...). - May partly dissociate in contact with humidity and release unpleasant smell - Min. 76.6 % butyrate-ANION and approximately 17% Calcium Sintobutyl Coating: incapsulates the active compound (Ca-butyrate) Fat components from vegetable origin ( Very good nutritional properties) • Fatty acids with high melting point •Hydrogenated fatty acids : C14 and lower (%) 1% C16 palmitic acid (%) 45 % C18 stearic acid (%) 53 % C18’oleic acid (%) 0.5 % C20 and higher 0.4% Sintobutyl (calcium butyrate) and Antibiotic Growth Promoters How Sintobutyl ranks between other claimed alternatives ? Sintobutyl versus Other . “Gut Modifiers” “Gut Flora Stabilisers” Are they all the same ? Encapsulated Feature / Effect Calcium-butyrate Yeast Components Botanical extracts (MOS, hydrolysed yeast) (herbs, roots,fruits) Probiotics,Prebiotics, enzymes acidifiers “coated”) GUT Morphology & Functioning (villi, epithelium, mucosa) GUT Micro flora - Bacterial Load - Metabolism, - Pathogens (C-Cl-Salm) DIRECT AGENT / NUTRIENT DIRECT INHIBITION Low MIC-value’s at intestinal pH = 6 In vivo flora studies IN-DIRECT EFFECT (some even stimulate butyric acid, -producing bacteria) IN-DIRECT EFFECT - Attachment - VFA –production (BA) - Substrate interaction IN-DIRECT EFFECT + and - DIRECT / INDIRECT EFFECT + and - More Feed Additives claim, support BUTYRATE effects Non Digestible Oligosaccharides Bacterial shift (LAB, Bifido) F.O.S. Fermentation to VFA and more Butyric (Megasphera LA -> BA) (inuline, profeed) Immuno-stimulant M.O.S. (yeast cell walls) Butyrate (butyric acid) Some induce BA production () MCFA’s Selective bacterial inhibition at intestinal, ceacal level : Coli, Clostridium, Salmonella Stimulation of enzyme synthesis Bacteria attachment (lectins) Herbal Extracts Protection and regeneration of intestinal villi (mucosa integrity) Part is converted at intestinal level to Butyric Stimulation of immunity Zootechical effects : FI, DWG, FCR, Egg Shell strength So, why not adding butyrate (Sintobutyl) directly !!??!! Mode of action of PROGUT (Vuorenmaa J & Vaahtovua J. (2006) PROGUT = Hydrolysed brewery yeast product; Prebiotic effects + Yeast Cell Wall effects are claimed - Stabilize gut flora - Support natural immunity - Prevent attachment of E.Coli, Salmonella to mucus Increases the MBI with piglets and poultry !!! Bifidobacteria + butyric acid producing bacteria MICROBIAL BALANCE INDEX = --------------------------------------------------------------Enteric group bacteria + bacteroides Significant correlation with DWG and FCR MBI Means more Butyrate in the gut, so just give straight Sintobutyl !!! Comparative mode of action and benefits of : ABGP ButyProl Coated MOS FOS MCFA Benzoic E.O. Butical Acids YCW’s Acid Herbs +++ -- +/- -- + /- -- +/- • Gut integrity -/+ • Enzyme synthesis -- ++ -- - - -- -- -- +/- • Immunity -- ++ -- + +/- -- -- +/- • Microbial Shift (beneficial) ++ +++ + + + colon +? ? ++ • Metabolic activity flora +++ + - - -- + colon +? ? ? • Inhibition - Coli indirect direct ++ - Clostridium ++ / - - ++ - - - Salmonella --/+ +++ +++ • Digestibility of nutrients + + + - + -- +++ +++ +? + ++ ++ • Pathogens --/+ ++ + ++ • Litter quality - /+ ++ - - • Absorption • FCR • Intestinal disorders ++ indirect + colon -- -- --- ++ direct +? + + -? -? +? -? -? -- -? + +? -/+ -/+ (c) -?+ -? -- + -- -? +? + ++ + + + ++ ++ +?- + + ++ -- -/+ -? +/- -/+ Comparative mode of action and benefits of : ABGP ButyProl Probiotics Butical • Gut integrity -/+ +++ +/- • Enzyme synthesis -- ++ - - • Immunity -- ++ +/- • Microbial Shift (beneficial) ++ +++ + • Metabolic activity flora +++ + - - • Inhibition - Coli indirect direct indirect - Clostridium ++ / - - ++ -/+ - Salmonella --/+ +++ --/+ + + -- - + -- +++ +++ indirect + ++ -- /+ • Pathogens --/+ ++ --/+ • Litter quality - /+ ++ -- • Digestibility of nutrients • Absorption • FCR • Intestinal disorders ++ Sintobutyl versus Aromabiotic (medium chain fatty acids) in rabbits Totally untrue !!!!!!!!!!! Pure Marketing !!!!! Sept 06 : so far limited use in 2-3 countries of EU-25 and on the way back (“fashion”) Ca-butyrate (Sintobutyl) versus MCFA’s CLAIM-ACTIVITY MCFA Calciumbutyrate Bacterial Inhibition MCFA soluble both in water and lipids, which would influence the speed of penetration of the product through the bacterial cell wall. Molecules have medium length C10-C14 and may be quite big to penetrate. Butyric acid is also soluble in water and in fat, both lipofylic and hydrofylic. On top the molecule is smaller (C-4), which normally could be easier to penetrate. E. Coli 1.0-1.5 log reduction (10-15 days) at 0.2 % - MIC = 0.5% !! 1.0 -1.2 log reduction (25-50 mmol) – J . Decuyper 2003-U.G. Clostridium MCFA would inhibit lipase production by bacteria, which seems needed for bacteria to attach to the gutwall. So attachment may be hindered and bacteria lessivate !? INDIRECT effect Villi integrity Performance (dwg,fcr) Calciumbutyrate has a DIRECT inhibition effect at pH=6 on all pathogenic clostridium strains (A.Decostere). Inhibtion of anaerobes by 0.5 log (J. Decuyper) MCFA would Increase villi length and vili/crypt ratio, but this is again INDIRECT (as more additives may do by fermentation or transformation to butyric acid) Butyrate is the FUEL (nutrient) of the gutwallcell (villi), having a DIRECT effect on the gutwall integrity and regeneration. Besides systemic effect, also the topical effect (local) Effects seems limited, nihil to negative (on feed intake). Few data ! Significant Positive Effect (higher feed intake -attractant). Full data base ! Butyrate – MCFA’s : similarities & differences !? Property, advantage Specific Characteristics Chain length pK-value MCFA’s caproic 4.88 Solubility Butyrate (butyric acid) C6, Caprylic C-8, Capric C10 4.89 4.89 fat and water soluble ME C4 (longest SCFA) 4.86 fat and water soluble 26.6 kJ/gr 17.4 kJ/gr Human application as functional lipid (“slimming”) as anti-cancer (colon) Absorption enhancing (paracellular permeability) enhancing (idem +emulsifyer) Bacterial Inhibition mg/ml E. Coli >5 2 5 < 5.0 (UG-AF) Salmonella >5 3 >5 < 5.0 (UG-VF) Clostridium >5 1-2 1 4-16 (UG-VF) C-12 = 0.1-0.2 Butyrate – MCFA’s : similarities & differences !? Property, advantage Specific Characteristics Ketosis effects (negative !!) Association with C-4, VFA =>Compatible with FOS,YCW, MCFA’s Risk : C6-C8 in neonatals (piglets) Antagonist (drop in C-4, VFA) NOT Butyrate (butyric acid) not (only in ruminants) Synergistic (= or >) YES Some Probiotics, .... Risk of lipolysis in feed Real NOT (lipase) Required antimicrobial 3-5 gr/l pure, stomach, gut concentration FI piglet 300 g/d => 10-17 kg per ton pure X 2 = 20-34 kg per ton of feed Accumulation in fat at high dosages (4 %) 0.5-3.0 kg/ton NOT MCFA’s = Butyrate antagonist !!!!! – Conflicting – Worrying ??? 1) J. Goris (2006), ILVO : C8 or caprylic acid changes fermentation profile in caecum of piglets : increase lactate, decrease butyrate and propionate (reversible) 2) F.Boyen & Pasmans (2006) – Effect on salmonella invasion of caprylic and caproic acid + butryic acid is antagonistic. Butyric alone decreases invasion ! 3) Leeson & Antongiovanni (2005) – Triglycerides of mcfa + butyric less effective in broilers than Triglycerides of butyric acid alone. 4) Van Oeckel (2005) - ILVO – Piglets trial : performance of combination of mcfaproduct + butyrate less good than mcfa, butyrate, but also than negative control. 5) Maertens L (2006) – ILVO – Rabbits : mcfa-product decreased significantly VFA’s and Butyric concentration in caecum. Unbalancing cecal flora !!! Salmonella invasion through epithelial cells of broiler chickens after treatment with butyric acid or MCFA (caproic acid) IN VITRO !! “MCFA seem to decrease invasion at least to the same extent as butyric acid but at lower concentrations” F. Van Immerseel et All (2004) – Appl. Environ.Microbiol. 6/2004 : 3582-3587 - In Vitro data : what happens in intestine with additive ? How much caproic acid is liberated from coconut-oil ? - Related only to eventual accumulation in liver and spleen, not in caecum (see in vivo test) Salmonella in different organs of broiler chickens after treatment with butyric acid or MCFA (caproic acid) Log cfu/gr CECUM-controle CECUM-treatment LIVER controle LIVER-treatment SPLEEN-Controle SPLEEN-Treatment 9 8 7 6 IN VIVO !! -1.66 log 5 4 -2.2 log 3 2 1 0 a b a’ a’ a” 1,56 kg Butyric = 3 kg Butical 60 a” a b a’ b’ a” a” 3,0 kg caproic acid = 6-30 kg MCFA-product ?? Inoculation with 10exp3 Salmonella Enteritidis on day 5, counts on day 8 (Van Immerseel - University Ghent) Composition of a commercial MCFA product Method : saponification BF3/MeOH (hot) BF3/MEOH (cold) + BF3/MeOH (hot) Fatty Acid % rel g/100 gram Caproic C6:0 8.1 5 8.6 5 6.9 3 Caprylic C8:0 62.1 32 60.8 30 59.6 23 Capric C10:0 29.4 15 30.2 14 33.0 12 Undecanoic C11:0 0.2 0 0.2 0 0.3 0 Lauric 0.2 0 0.2 0 0.2 0 C 12:0 53 % rel g/100 gram % rel 49 Sample from Belgium – 2004 ; Independent industrial laboratory, analysis in 2005 g/100 gram 38