Coated calcium butyrate in calf milk replacers: mode of action, application and benefits Dr. Noémie Van Noten – Sanluc International
Presentation overview 1. Introduction on butyrate 2. Mode of action 3. Benefits 4. Application 5. Experimental part 6. Conclusions
1. Introduction
Endogenous butyrate production Butyric acid = product of bacterial fermentation of dietary fiber: o in the rumen of ruminants o in the hindgut of monogastrics and ruminants
Cui et al. (2019). Compr. Rev. Food Sci. Food Saf. 18: 1514-1532.
1. Introduction
Butyrate supplementation o Milk fat contains ± 4-5% butyric acid o But, calf milk replacer: Ø Vegetal or animal fat Ø Low butyric acid content
Calcium
o Butyric acid: Ø Volatile Ø Unpleasant odour Ø Liquid
→ Supplementation as (coated) Ca-salt (CH3-CH2-CH2-COO)2-Ca
2. Mode of Action
Molecular Mechanisms Energy source
Butyric acid
Signaling molecule: GPRs
Epigenetic regulation: HDAC
2. Mode of Action
Butyrate as energy source ATP
Colonocyte
o Butyrate = preferred energy source of colonocytes o Only small fraction of luminal butyrate enters the blood
Portal vein
circulation o Uptake in liver almost complete: energy
Liver
2. Mode of Action
Molecular Mechanisms Energy source
Butyric acid
Signaling molecule: GPRs
Epigenetic regulation: HDAC
2. Mode of Action
Butyrate as signaling molecule Butyrate interacts with G protein-coupled receptors (GPRs) = transmembrane proteins that detect molecules outside the cell and activate cellular responses Involved in: • sensing luminal contents • intestinal motility • secretion of hormones • innate immunity
Liu et al. (2018). Adv. Nutr. 9:21-29
2. Mode of Action
Molecular Mechanisms Energy source
Butyric acid
Signaling molecule: GPRs
Epigenetic regulation: HDAC
2. Mode of Action
Butyrate as epigenetic regulator Histone Deacetylases (HDACs) o Enzymes o Remove acetyl groups from peptide chains o Affect mainly histones (DNA-packing) o DNA becomes condensed and silenced
Butyrate = HDAC inhibitor o Histone tails remain acetylated → Genes remain active → Affects a large amount of genes → Essential for gut homeostasis Stilling et al. (2016), Neurochemistry International 99, 110-132
3. Benefits Molecular Mechanisms
Triple mode of action
Energy source
Butyric acid Signaling molecule: GPRs
Epigenetic regulation: HDAC
Gut Physiology and Digestion
Inflammation control
Butyric acid
Microbiota Modulation
3. Benefits
Gut Physiology and Digestion o Cell proliferation ↑, apoptosis ↓ Ø Longer intestinal villi Ø Rumen papillae development
o Activity of digestive enzymes↑:
Control
Butyric acid
Ø Brush border enzymes Ø Pancreatic enzymes
o Improved intestinal barrier function
Improved digestion and absorption Mentschel et al. (2001), Archives of Animal Nutrition, 55(2), 85-102.
3. Benefits Molecular Mechanisms
Triple mode of action
Energy source
Butyric acid Signaling molecule: GPRs
Epigenetic regulation: HDAC
Gut Physiology and Digestion
Inflammation control
Butyric acid
Microbiota Modulation
3. Benefits
Inflammation control and immunomodulation o Inflammation reduction Ø Regulation of pro- and anti-inflammatory mediators (IL, PPAR-γ ) Ø Increased heat shock protein expression Ø Upregulation of antioxidant enzymes
o Immune regulation Ø Less excessive innate immunity Ø More specific immune reactions
Disease resistance ↑ & nutrients for growth↑ Parada Venegas et al. (2019). Frontiers in immunology, 277.
3. Benefits Molecular Mechanisms
Triple mode of action
Energy source
Butyric acid Signaling molecule: GPRs
Epigenetic regulation: HDAC
Gut Physiology and Digestion
Inflammation control
Butyric acid
Microbiota Modulation
3. Benefits
Modulation of Microbiota o Mutual relationship Ø Microbiota composition ↔ butyric acid concentration Ø Firmicutes / Bacteroidetes-ratio ↑
o Pathogen control Ø Directly or indirectly Ø Salmonella, Clostridium perfringens, E. coli
3. Benefits
Improved PERFORMANCE
Triple mode of action Gut Physiology and Digestion
Inflammation control
Butyric acid
Microbiota Modulation
4. Application
Digestion of newborn calf Young calf = pre-ruminant o Milk bypass via esophageal groove o Rumen, reticulum and omasum do not work o Enzymatic milk digestion in abomasum o Rumen development : Ingestion of solid feed
4. Application
Butyrate Supplementation Rearing calves
Veal + Rearing calves
Solid Feed
Milk Replacer
Uncoated CaBut
Coated CaBut
Uncoated CaBut
Coated CaBut
Release: abomasum Effect: Abomasum pancreas prox. SI
Release: gradual Effect: Abomasum pancreas prox. SI distal SI
Release: rumen Effect: Rumen
Release: gradual Effect: Forestomach Abomasum prox. SI
5. Calf trials 1. Intestinal morphology 2. Veal calves – Germany 3. Veal calves - Belgium
5. Experimental part: trial 1
Gut morphology calf trial Protocol: o o o o
50 calves with average age of 94 days Pre-trial: 3 days on conventional milk powder Trial diets: 12 days Dietary treatments: Ø T1: Conventional milk replacer (CMR) Ø T2: Modified milk replacer (MMR) with 8% soy protein Ø T3: MMR + 1,28 kg/ton coated calcium butyrate (CCB) Ø T4: MMR + 2,56 kg/ton CCB Ø T5: MMR + 5,12 kg/ton CCB
5. Experimental part: trial 1
Small intestinal morphology Jejunum Villus height (µm)
2000 1500
1305
❷
❶ 1131
1241
1380
1511
MMR
1000
MMR+1,28CCB MMR+2,56CCB
500 0
CMR
MMR+5,12CCB b
c
bc
ab
a
❶ MR with soy protein significantly reduces intestinal villi height ❷ CCB increases intestinal villi height in a dose dependent manner
5. Experimental part: trial 1
Small intestinal morphology
CMR MMR + 1,28 CCB
MMR MMR + 2,56 CCB
MMR + 5,12 CCB
5. Experimental part: trial 2
Calf trial - Germany Protocol: o 30 male calves (German Holstein); housed individually o Trial period: Ø d9-d11 of age: adaptation period Ø d12-d68 of age: trial period (56 days) o Feeding regime: calf milk replacer + calf starter + straw o Dietary treatments: Ø Control group: basal milk replacer Ø CCB group: basal milk replacer + 2,58 kg/ton CCB
5. Experimental part: trial 2
Calf trial - Germany 100
Body weight (kg)
Results:
+2,3%
70,8
80 60
50,8
94,3
96,5
b
a
72,8
50,6
40 20 0 d0
d21 Control
d56
CCB
o No differences in feed intake o Significant improvement of FCR: Ø Control: 1,927 -4,5% Ø CCB: 1,840
5. Experimental part: trial 3
Calf trial - Belgium Protocol: o o o o
50 male calves (Holstein Friesian); housed individually Age at arrival: between 10 and 14d Trial period: 56 days Feeding regime: Ø d0-d18: calf milk replacer + calf flakes Ø d19-56: calf milk replacer + concentrate enriched with roughage
o Dietary treatments: Ø Control group: basal milk replacer Ø CCB group: basal milk replacer + 2,50 kg/ton CCB
5. Experimental part: trial 3
Calf trial - Belgium
+2,2%
Results:
88,3 90,2
80 60
45,5 45,5
49,6 49,6
d0
d14
60,2 61,1
72,5 73,5
40 20 0 Control
d28 CCB
d42
1000 800
d56
1126 1191
1200
ADG (g/d)
Body weight (kg)
100
760 824
877 884
d14-28
d28-42
+4,5% 764 798
600 400
291 292
200 0 d0-d14
d42-56
d0-56
5. Experimental part: trial 3
Calf trial - Belgium
+2,9%
1000
Results: ADFI (g)
800
741
752
741
774
600 400 200 0 Milk powder Control
Concentrate CCB
o Significant improvement of FCR: Ø Control: 1,953 -3,2% Ø CCB: 1,890
6. Conclusions
Coated calcium butyrate in calves o Dose recommendation: Ø Milk powder: 1 - 3 kg/ton Ø Solid starter feed: 1,5 - 2 kg/ton
o Benefits: Ø Ø Ø Ø Ø
Improved intestinal, morphology and health Less diarrhoea and intestinal problems Improved weight gain and FCR Extensive development of rumen papillae Faster and higher prestarter feed intake
Early development of a functional GIT resulting in high performing and healthy calves
Coated calcium butyrate in calf milk replacers: mode of action, application and benefits Thank you for your attention!