enhancing calf gut health · dietary regimes in early life influence lifetime productivity 1kg of...
TRANSCRIPT
Enhancing Calf Gut Health
Michael A. Steele, Department of Animal Biosciences
I. Calf Management Trends
II. Colostrum
III. Plane of Nutrition
IV. Weaning
V. Antimicrobial (SCB Story)
Enhancing Calf Gut Health
(Adapted from Conrad’s Waddington epigenetic landscape)
“…early adaptation to a stress or stimuli that permanently changes the physiology and metabolism of the organism and continues to be expressed even in the absence of the stimulus/stress that initiated them…”
(Patel and Srinivansan, 2002)
“Nutritional Programming”
Dietary regimes in early life influence lifetime productivity
1kg of pre-weaning ADG = 1,540 kgs of milk in first lactation
(Soberon et al., 2012)
Early Life Nutrition
Gut Health and Dairy Calves
Mortality and Morbidity:
5% mortality, 32% due to digestive disorders
Mean age: 18.3 ± 2.3 d old
12.1% of calves failed passive transfer
26.8% of calves receive antibiotics
48.4% for digestive disorders
Immune Status:
Antibiotic Use:
(Shivley et al. 2018)
(Urie et al. 2018)
38% morbidity, 56% due to digestive disorders
Pre and Post-WeaningPre-ruminant Ruminant
Milk Solid Feed
Weaning Transition
1 wk 4 wk 8 wk 12 wk
Pre and Post-WeaningPre-ruminant Ruminant
Milk Solid Feed
Weaning Transition
1 wk 4 wk 8 wk 12 wk
Mixture of absorptive, goblet, paneth and neuroendocrine cells
Microbial richness and diversity increases through the lower gut
Cell junction proteins are expressed differentially (Malmuthuge et al., 2012)
Gut Epithelium
(Steele et al., 2016)
104/mL 1010/mL1010/mL
Industry Concerns
AntimicrobialMaternal
Colostrum Plane of Nutrition
Knowledge Gaps
Industry Concerns
AntimicrobialMaternal
Colostrum Plane of Nutrition
Knowledge Gaps
(Sharifi et al., 2009)
Bottle Tube
Colostrum Feeding Method
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10
20
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40
0 120 240 360 480 600Co
nce
ntr
ati
on
(m
g/L
)
Time Relative to Colostrum Feeding (minutes)
Acetaminophen
Bottle
Tube
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0 500 1000 1500 2000 2500
Me
an
IgG
Co
nc.
(m
g/m
l)
Time Relative to Colostrum Feeding (minutes)
BottleTube
IgG
Colostrum Feeding Method
(Desjardins-Morrissette et al., 2018)
Delayed Colostrum Feeding
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5
10
15
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25
30
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
0 h 6 h 12 h
(Fischer et al., 2018)
IgG
mg/ml
Hours after birth
0.0
1.0
2.0
0h 6h 12h
Pro
po
rtio
n (
%)
Treatment
Bifidobacteria associated with colon mucosa
a
ab
b
0.00.10.20.30.4
0h 6h 12h
Pro
po
rtio
n (
%)
Treatment
Lactobacillus associated with colon mucosa
aab
b
Delaying the first colostrum meal may delay the colonization of
beneficial bacteria to the calf intestine
(Fischer et al., 2018)
Delayed Colostrum Feeding
Heat Treatment of Colostrum
0
0.1
0.2
0.3
0.4
0.5
NC FC HC
Pro
po
rtio
n o
f B
ifid
ob
act
eri
um
6hr 12hr
aa
b
x
y
xy NC = No Colostrum
FC = Fresh Colostrum
HC = Heated Colostrum
Heat-treated colostrum increases Bifidobacterium and reduced the colonization of E. coli in the small intestine
(Malmuthuge et al., 2015 )
0
500
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1500
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3000
3'SLN 6'-SLN 3'-SL 6'-SL DSL
Co
nce
ntr
ati
on
(µg
/g)
Bovine Colostrum Oligosaccharide
Fresh Colostrum
Heated Colostrum
Heat-treatment may cleave prebiotic oligosaccharides from colostral proteins and lipids
(Fischer et al., 2018)
Heat Treatment of Colostrum
0
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6SL 6SLN DSL 3SL
Co
nce
ntr
atio
n (μ
g/m
l)
Oligosaccharide
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14
Oligosaccharides – Transition*
*
*
* * *
*
*
*
Bovine colostrum oligosaccharides (bCOs) produced in higher concentrations in milkings 1-3 compared to milking 8+
Multiparous cows have higher concentrations of 6’SLN compared to primiparous (Fischer et al., 2020)
First Feeding Wk 1
Colostrum Solid Feed
Transition
First Feeding
Colostrum Milk
Wk 1
Milk
From Colostrum to Milk
All calves fed one meal of colostrum followed by:
Milk
50% milk/ 50% colostrum (Transition)
Colostrum (Pyo et al., 2020)
Milk 50%/50% Colostrum
From Colostrum to Milk
(Hare et al., in review)
IgG
mg/ml
Hours after birth
0
10
20
30
40
0 2 4 6 8 10 12 14 16 18 20 22 24
Second Meal
First Meal
Milk 50%/50% Colostrum
From Colostrum to Milk
Passive Transfer Trancytosis of immunoglobulins
(Jochims et al., 1997)
Receptor mediated and highly regulated
Trancytosis (to blood)
Recycling (back to lumen)
Metabolism (endosome)
Regulation of these pathways in calves is unclear
Endosome Formation
Basal Membrane Release
Recycled to Lumen
Metabolized
Pinocytosis
Industry Concerns
AntimicrobialMaternal
Colostrum Plane of Nutrition
Knowledge Gaps
Normal Pre-Weaning Milk Intake
(de Passille et al., 2016) (Jasper and Weary, 2002)
d4 of life
Feeding Large Meals
Calves typically nurse 6-12 times per day in the first weeks of life (Jensen, 2004)
Larger meals fed less frequently increase the risk of: Abomasal inflammation & lesions
Milk overflow into the rumen
Ruminal acidosis, decreased passage rate and digestion
(Berends et al., 2012; 2015)
Inflamed
Abomasum
0
5
10
15
20
25
0 60 120 180 240 300 360 420Ace
tam
ino
ph
en
(m
g/L
)
Time (min)
Larger Meal Size and Insulin Sensitivity
Compared calves fed elevated (8L/d) vs low (4L/d) plane of milk 2x per day
No evidence of post-prandial hyperglycemia and hyperinsulinemia
No difference in glucose tolerance
Slower (41% reduction, P = 0.02) abomasal emptying rates during the pre-weaning phase
(MacPherson et al., 2016)
Elevated, KSB = 0.21Low, KSB = 0.34
Gastric emptying rate will influence glucose appearance in blood
(Stahel et al., 2016)
0
2
4
6
8
10
0
10
20
30
0 100 200 300 400
Glu
cose
(Mm
) an
d
Insu
lin
(ng
/ml)
Ace
tam
ino
ph
en
(m
g/m
l)
Time (min)
Glucose
Insulin
Acetaminophen
Gastric Emptying and Glucose-Insulin Dynamics
Glucagon-like Peptides
Proliferation
Nutrient absorption
Gut motility
Blood flow
Gut Permeability
Milk Replacer vs Whole Milk Most MR are high in lactose and osmolarity, low in fat compared with whole milk
0%
20%
40%
60%
80%
100%
Milk MR
other
ash
protein
fat
lactose
18%
45%37%
31%
300 mOsmwhole milk /body fluid
400-600 mOsmMR
Hypertonic MR increases gut permeability (Wilms et al., 2019)
Higher lactose results in increased gastric emptying and lower glucose tolerance in the first week of life (Welboren et al., in review)
Weaning Challenges A smooth transition from a monogastric to a ruminant
Decreases morbidity and mortality and increases gain (Khan et al., 2012)
Requires adequate size and function of the rumen (Baldwin, 2004)
Elevated plane of nutrition pre-weaning makes weaning more challenging (Khan et al., 2011)
Pre and Post-WeaningPre-ruminant Ruminant
Milk Solid Feed
Weaning Transition
1 wk 4 wk 8 wk 12 wk
Abnormal GIT Development Ruminal parakeratosis is
common during weaning(Bush, 1965)
Ruminal acidosis has been documented however to date, no research has linked it to impairment of gut health (Laarman et al., 2012)
Parakeratosis
Is ruminal acidosis good or bad for the calf?
0
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800
1000
1200
1400
1600
5 6 7 8 9 10 11 12
tim
e b
elo
w t
hre
sho
ld (
min
/d)
pH 5.8
pH 5.5
pH 5.2
week
6 week wean
Ruminal pH During Weaning
(Kohler et al., in preparation)
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tim
e b
elo
w t
hre
sho
ld (
min
/d)
surfacearea
pH 5.8surf
ace
are
a (
µm
2 )
week
6 week wean
Ruminal pH During Weaning
(Kohler et al., in preparation)
Ruminal Gene Expression
3063 557
Common genes are predominately metabolic Ketogenesis
Fatty acid metabolism
It takes time for the genes involved in structural adaptations to change
(Kohler et al., in preparation)
Early and Abrupt Weaning
Pre-ruminant Ruminant
Milk Solid Feed
Transition
Pre-ruminant Ruminant
Milk Solid Feed
Weaning Age
0
2
4
6
8
10
1 8 15 22 29 36 43 50 57 64
EarlyLate
Calf Age (Eckert et al., 2015)
L/d
30
40
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60
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90
100
110
0 7 14 21 28 35 42 49 56 63 70
EarlyBW
(kg)
6 week wean
Calf Age (Eckert et al., 2015)
Weaning Age - Bodyweight
30
40
50
60
70
80
90
100
110
0 7 14 21 28 35 42 49 56 63 70
Early
Late
6 week wean
8 week wean
* **
**P<0.05*
Calf Age (Eckert et al., 2015)
Weaning Age - Bodyweight
BW
(kg)
(Eckert et al., 2015)
Weaning Age – ME Intake
0
500
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1500
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3500
4000
35 42 49 56 63 70
Weaning Strategy – Delayed WeaningImpact on Ruminal Development
Calf Age (d)
Weaning Strategy – Delayed WeaningImpact on Ruminal Development
Wean
6 wk wean
8 wk wean
Wean
Post-weaning
(Meale et al., 2016)
Pre-weaning
L/d
Calf Age (d)
0
1
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3
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10
0 6 12 18 24 30 36 42 48 54
Step-Down
Abrupt
Step-Down Weaning
(Steele et al., 2017)
30
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90
100
0 6 12 18 24 30 36 42 48 54
Step-Down
Step-DownWeight (kg)
Weaning
Calf Age (d)
Step-Down
Step-Down - BodyweightP<0.05
(Steele et al., 2017)
30
40
50
60
70
80
90
100
0 6 12 18 24 30 36 42 48 54
AbruptStep-Down
*
Weight (kg)
Calf Age (d)
*
Step-Down - BodyweightP<0.05
(Steele et al., 2017)
WeaningStep-Down
0
2
4
6
8
0 6 12 18 24 30 36 42 48 54
AbruptStep-Down
Intake (Mcal/d)
Calf Age (d)
Weaning
Step-Down
Metabolizable Energy Intake
(Steele et al., 2017)
0
500
1000
1500
2000
2500
30 36 42 48 54
-0.3 -0.2 -0.1 0.0 0.1 0.2 0.3
-0.3
-0.2
-0.1
0.0
0.1
0.2
0.3
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PCoA plot_weighted unifrac distance
PC1 Percent variation explained 17.8%
PC
2 P
erce
nt v
aria
tion
expl
aine
d 9.
1% Abrupt_post-weaning
Abrupt_pre-weaning
Step-down_post-weaning
Step-down_pre-weaning
(Meale et al., 2016)
Weaning Strategy – Abrupt WeaningImpact on Ruminal Development
Calf Age (d)
Pre-weaningPost-weaning
Wean
Gradual
Abrupt
Pre and Post-WeaningPre-ruminant Ruminant
Milk Solid Feed
Weaning Transition
1 wk 4 wk 8 wk 12 wk
Fecal microbiota displayed more diversity post-weaning (Meale et al., 2015)
0
2
4
6
8
10
36 48 54
** P = 0.04
Abrupt Weaning – Delayed WeaningImpact on Hindgut
Calf Age (d)
Fecal Starch %
Step-down
Abrupt
Wean
Diversity in Fecal Scores
Barrier Function at Weaning Starter feeding in calves decreased the expression of
tight junctions (Malmuthuge et al., 2012)
Weaned (d 40)
Not Weaned
(Wood et al., 2015)
Barrier Function at Weaning Weaning related changes of the gut epithelium (Pletts et al., in review)
Not-Weaned, d 42
Weaned, d 42
Rumen Duodenum
Endoscopic Biopsy
Post-Weaning and Beyond An area that has not been studied
Need to integrate pre and post weaning planes of nutrition with lifetime performance
Industry Concerns
AntimicrobialMaternal
Colostrum Plane of Nutrition
Knowledge Gaps
Potential Mechanisms of Actions of Saccharomyces cerevisiae boulardii
(SCB)
1st line of defense:Intestinal microflora
3rd line of defense:Intestinal immune system
2nd line of defense:Intestinal epithelia
Anti-inflammatory
properties, immune cells
recruitment, cytokine
production, etc...
Intestinal permeability, mucin
production, antimicrobial peptides,
etc...
Reinforcement of
positive microflora : LAB,
cellulolytic bacteria…
42 calves from d2 to d54
2 groups: CON and SCB fed MR + starter ad libitum
No difference on performance and health between CON and SCB
BUT: overall health = very good
adequate passive transfer, clean environment, no transportation
Looking at more challenging conditions closer to on-farm reality
Study 1: Pre-weaning
(He et al., 2017)
Study 2: Veal farm 2 groups: CON & SCB fed MR only
Back to basics: verification of the successful supplementation of SCB
Copy number of 26S rRNA Saccharomyces cerevisiae gene/g of feces
0.0
0.5
1.0
1.5
2.0
2.5
0 2 7
CON
SCB
TRT = 0.032
Week = 0.001
TRT*Week = 0.008
10
7copy n
um
ber/
g
Week
Reduction in fecal score and total cases of diarrhea
Study 2: Veal farm challenge
0
10
20
30
40
50
1 2 3 4 5 6 7
Week of experiment
*
*
Total # of diarrhea cases
0.6
0.7
0.8
0.9
1
1.1
1.2
1 2 3 4 5 6 7
Week of experiment
*
**
Fecal score
* P < 0.05* P < 0.05
(Villot et al., 2019)
Study 2: Veal farm challenge No big changes highlighted in microbiota composition of feces
Difficult to understand the mechanisms of action with on-farm experiment
(Villot et al., 2019)
Initial health status
Transportation
Housing conditions
Antibiotic treatment
New strategy:
Start treatment at birth
Supplementation from colostrum feeding in controlled conditions
Investigation of the gut with dissection
Looking at microbiota + host response
Confounding factors?
Study 3: Neonate
Dr. Clothilde Villot
Endoscopic biopsy
Study 3: Neonate
d0 d1 d2 d3 d4 d5 d6 d7
Remove from the dam
directly after birth
h2 h12 19:00
B
I
R
T
H
Milk Replacer 17% of BW
+ SCB/Control
7:00 07:00
…
E
U
T
H
A
N
A
S
I
A
Fecal sample & score & body temperature
Dissection
Passage of nutrients
7:00
10:00
7:00
Blood sample
Milk Replacer 15% of
BW
+ SCB/Control
Colostrum
+
SCB/Control
GUT Permeability
Study 3: Neonate Colon biopsy technique:
Non invasive Repeated measurements Good quality of samples
Measurements: Bacterial composition with qPCR & DNA sequencing (16S amplicon) Genes expression of the host with total RNA sequencing
(Van Niekerket al., 2018)
H&E stain
Recovery of Cr in urine, %
CON (mean ± SE)
SCB(mean ± SE)
P-Value (Student Test)
Day TRT TRT * Day
Day 2 3.01 ± 0.12 3.44 ± 0.15 NS 0.863 NS
Day 6 3.40 ± 0.19 2.53 ± 0.08 0.080
Gut permeability test
No difference of gut permeability in d2 and d6
Gut permeability tends to be improved at d6 for SCB calves
Study 3: Neonate
Study 3: Neonate
Provides mucosal immune protection in a non-inflammatory manner
Promotes the maintenance of appropriate bacterial communities
Neutralization of incoming pathogens and microbial inflammatory products, and facilitates antigen signaling
(Mutwiri et al., 1999)
Immunoglobulin A
Immunoglobulin A Production
0
0.5
1
1.5
2
2.5
Jejunum Ileum Colon Feces
IgA mg/g Dry Matter
**
Endogenous production of IgA in the gut of 7d old calves IgA production in ileum SCB seems to stimulate IgA production
* P < 0.05
(Villot et al., in review)
Immunoglobulin A Production
Endogenous production of IgA in the gut of 7d old calves IgA production in ileum SCB seems to stimulate IgA production
(Villot et al., in review)
Take Home Messages There are still some basic concepts in calf biology and
nutrition that we do not understand
No difference between tube vs. bottle feeding colostrum for passive transfer
Delaying colostrum by six hours can impact passive transfer and gut microbiology
Pasteurizing colostrum may help to improve calf gut health if managed properly
Take Home Messages An abrupt transition from colostrum to milk can
compromise gut development
Elevated planes of milk can be fed early in life
Elevated planes of milk can be fed with 2x/day feeding schemes
Milk replacer formulations high in lactose may impact gut health and insulin sensitivity
Take Home Messages Weaning in dairy calves is one of the largest
transformations of the gut in nature
Weaning age and abruptness impact performance on high planes of milk nutrition
Weaning is also associated with gut health problems
Post-weaning nutrition is another area left undiscovered in calf nutrition
Direct fed microbials have potential to improve gut health in pre-weaned calves