Transcript Comparative MODE OF ACTION and EFFECTS in monogastric

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