Download How to boost piglet immune response with vitamin D

Piglet Health
How to boost
piglet immune
response with
vitamin D
he post-weaning phase is a critical period in a
piglet's life. The development of a strong immune
system at this early stage is key to securing its
health and future optimum performance.
However, a piglet has limited ability to mount and
regulate an immune response when it is weaned from the sow
at between three and five weeks old in commercial practice. Its
immunity needs to develop as the passive protection from the
sow's antibodies fade away and viral, bacterial and parasitic
infections are at their highest risk. Any compromise to a piglet
at this period has repeatedly been shown to impact negatively
on its later performance.
What is immunity?
In brief, immunology can be defined as the field of science that
studies the different mechanisms by which animals discern
between their own cells and foreign pathogens. There are two
different immune systems; the innate immune system and the
adaptive immune system. All animals are born with the innate
system, in which protection is always present. It includes
phagocytic (cells that eat other cells) macrophages and dendritic cells. In the adaptive system, protection arises by an
immune response, including humoral immunity producing
antibodies and cellular immunity producing white blood cells.
It learns to recognise pathogens and has very powerful effector
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PIG PROGRESS Volume 31, No. 5, 2015
functions which can inactivate or destroy most micro-organisms. During development of the immune system in embryogenesis, deficiencies of micronutrients (vitamins, fatty acids,
minerals, trace elements) are more critical than macronutrients. This 'organ', with an extremely high cell turnover, needs a
secure supply of nutrients (above all, proteins and vitamins)
and when engaged in defense against a pathogen its nutrient
demand is considerably increased. Studies are showing that
optimising feed intake of vitamin D can boost piglet immunity
in a number of different ways.
The changing face of vitamin D
Vitamin D is an essential nutrient which is routinely added to
animal feed, primarily because animals' blood levels of vitamin
D vary considerably. It has become the focus of renewed attention by nutritionists and swine producers worldwide in recent
years, because of findings that indicate that the benefits of vitamin D go beyond the archetypal function of the regulation of
calcium and phosphorus homeostasis and its effect on bone
development.
Vitamin D metabolites control the expression of more than 200
genes through activation of the vitamin D receptor, which regulates or modulates gene expression within the target cell. This
gives the vitamin a role in many functions in swine, including
immunity, muscle function and reproduction. The vitamin D
receptor is not only found in the intestinal enterocyte, the osteoblast, and the renal cells, but it is also found in a wide range
of cell types whose function does not relate to calcium metabolism, such as the intestine, pancreas, heart, eye, brain, thyroid,
parathyroid, muscle, or immune cells.
Better understanding of the functions that vitamin D has in
swine physiology allows producers to see the potential benefits
it could have on productivity and profitability.
How does vitamin D work?
The predominant form of vitamin D in animals is called chole-
Improved piglet immunity
The newborn piglet is exposed to a vast array of antigens from
the moment it is born. It relies on maternally-derived immunity for protection, until it develops its own active immunity.
Prior to weaning, sow's milk provides most of the nutrients
that the piglet will receive for maximal growth and health.
However, sow's milk provides little vitamin D. Supplementing
sows with vitamin D before birth could provide a nutritional
strategy to increase vitamin D status of the piglet, through placental transport or via sow's milk.
Figure 1 - Vitamin D metabolism.
7-dehydrocholesterol
Skin
Dietary Vitamin D3
UVB
irradiation
Figure 2 - Maternal supplementation.
7-dehydrocholesterol
Skin
Hy-D
25-OH-D3 concentration in blood plasma of suckling piglets (ng/ml)
Source: Weber and others, Journal of Animal Science, Feb 2014
UVB
irradiation
10
Commercially available calcifediol (Hy-D, DSM)
Vitamin D3
8.57
Cholecalciferol (Vitamin D3)
Liver
hydroxylation
25-hydroxycholecalciferol
(25-OH-D3, Circulating form)
Kidney
hydroxylation
Cholecalciferol (Vitamin D3)
Liver
hydroxylation
25-hydroxycholecalciferol
(25-OH-D3, Circulating form)
Kidney
hydroxylation
25-OH-D3 in plasma (ng/ml)
T
By Antoine Meuter, DSM
calciferol (D3), which is absorbed in the lymphatic system. It
then travels to the liver, where it is converted (hydroxylated) to
25-OH-D3 (calcifediol), the main circulating form of the vitamin. Once hydroxylated, the vitamin becomes more 'waterfriendly' and circulates more easily in the blood system.
However, the conversion from vitamin D to calcifediol cannot
be regulated easily, especially by adding more vitamin D to the
feed. This is because the liver acts as a 'bottle-neck' to vitamin
D, controlling circulating levels of calcifediol.
Once calcifediol reaches the kidneys, it is further hydroxylated
into a functional form of vitamin D, called 1,25-(OH)2-D3
(calcitriol), which is even more water-friendly. This compound,
made from this highly-regulated step of vitamin metabolism, is
actually a hormone that acts on intestinal cells to enhance calcium and phosphorus absorption for bone formation and other
bodily functions. Without vitamin D, dietary calcium and
phosphorus are poorly utilised. Studies show that immune cells
and muscle cells also require vitamin D for optimal function.
Rovimix Hy-D (DSM), is a commercial form of calcifediol. It is
absorbed more easily than pure vitamin D3 and it bypasses the
liver and reaches the blood stream quickly and efficiently.
Research reports have indicated that pigs supplemented with
calcifediol have higher circulating levels of calcifediol in plasma leading to better overall calcium homeostasis, increased
muscle development, and enhanced immune response compared to pigs fed with vitamin D3 (Figure 1).
Photo: Peter Roek
The benefits of vitamin D in pig feed
go beyond the well-known function of
calcium regulation and phosphorus
homeostasis and its effect on bone
development. Ongoing research
continues to unveil more modes of
action for pigs.
Studies are showing that optimising feed intake of vitamin D
can boost piglet immunity in a number of different ways.
8
6
6.06
5.07
3.97
4
2
1,25-dihydroxycholecalciferol
(Active form)
1,25-dihydroxycholecalciferol
(Active form)
0
week 3
weaning
PIG PROGRESS Volume 31, No. 5, 2015
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Photo: Jan Willem Schouten
A conventional way to get a lot of vitamin D: sunbathing.
Figure 3 - Cellular imune response in piglets.
Total cell numbers - Leukocytes/ml blood (left) and phagocytosis activity - % phagocytosis (right).
Source: Konowalchuck and others, 2013 Vet. Immun. Immunopathology
Internalised
10.0E+07
Surface-bound
Granulocytes *P<0.01
50
P=0.01
*P=0.04
P=0.03
*P<0.01
8.0E+06
40
6.0E+06
30
4.0E+06
20
2.0E+06
10
0.0E+00
control
Vitamin D
0
Hy-D
control
Vitamin D3
Hy-D
Figure 4 - Humoral immune response.
in piglets 21 days and 48 day after weaning
Source: Research station, France, 2013
Control
*
Serum concentration (mg/mL)
80
Commercially available calcifediol **
70
*
60
* P< 0.05
50
40
30
20
*
10
0
-
25
D3
OH
d
1d
G2
-
25
D3
OH
s
lin
bu dd
glo G21
d
8d
G4
o
un
m
Im
*
m
Im
s
lin
bu dd
glo G48
o
un
**Hy-D, DSM
Recently, a study (Figure 2) showed a higher level of calcifediol
in sow milk with a commercial calcifediol maternal diet compared to a standard vitamin D3 maternal diet, leading to a
higher concentration of vitamin D in the blood of the piglets
and allowing them be better equipped to face the critical weaning period. After weaning, the circulating humoral antibodies
persist and continue to provide effective protection against
invasion of the pig's body. However at weaning, milk, the
source of mucosal-associated antibodies is suddenly cut off.
The antibodies that are present in the mucous decline within a
day or so. In 2012, researcher Jeffrey D. Konowalchuk, of the
University of Alberta, Canada, carried out a study which
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PIG PROGRESS Volume 31, No. 5, 2015
'looked to support previous observations regarding the positive
immunomodulatory role of vitamin D and indicates that commercial calcifediol is a superior dietary supplement for weanling piglets. After two weeks of nutritional supplementation, it
was found that the diet with commercial calcifediol led to the
greatest increase in the concentration of serum 25(OH)D3,
compared to control and vitamin D3-supplemented diets. An
average of 40.4 ng/ml of 25(OH)D3 was found in the serum of
animals supplemented with the additive, compared to 11.2
(vitamin D3 group) and 7.87 ng/ml (control diet group). In
practical swine production, a plasma concentration below 10 to
15 ng 25(OH)D3/ml, is normally considered as deficient.
White blood cell numbers
Systemic blood and peripheral bronchoalveolar mucosal compartments known to serve as portals for the infiltration of
pathogens into the animal host were thus affected. This resulted in an increase of white blood cell numbers, upregulation of
their survival capacity and an increase in the phagocytic antimicrobial capacity of discrete cell populations (Figure 3).
A rise in white blood cells can have a positive impact in the
capacity of animals to mount effective immune responses
against incoming pathogens. Upregulation of immune competence status was therefore evident two weeks after initiation of
diet supplementation in weaned pigs and was correlated with a
parallel increase in serum levels of 25(OH)D3 in response to
supplementation with commercial calcifediol.
Experimental study
The positive regulation of piglet immune response with the
same calcifediol additive was confirmed in another experimental study carried out in France's western region, where its
impact on humoral immune parameters was measured. As
shown in the graph (Figure 4), the diet containing the additive
did not only significantly impact the 25(OH)D3 plasma concentration but also the immunoglobulins G (major component
of humoral immunity) blood levels. The immune system is a
double-edged sword, as pathogen elimination is important, but
the immune response costs energy. It was therefore interesting
to observe in this experiment that a higher stimulation of the
immune system did not negatively impact piglet zootechnical
performance with both piglet groups (additive and vitamin
D3), having similar feed conversion ratio and average daily
weight gain. The results showed that efficient immune
response is critical and vitamin D is critical to this.
Future performance
Today, specialised nutritional supplements of sows and progeny play a vital role in piglet health. This is extremely important
for swine producers to ensure future performance and productivity of their animals. These new studies provide important
support for the significant immunomodulatory impact that
vitamin D3-derived nutritional regimes have on swine at weaning. These results should contribute to the development of
improved strategies for the management of weanling pigs in
commercial environments, where they are known to be particularly susceptible to disease.
References available upon request.