• BovineColostrum

The Bovine Colostrum: importance in calf growth and potential use in the treatment of gastrointestinal diseases

Introduction: The Colostrum

We have referred to the colostrum while citing colostral immunity during the lectures in the chapter of Immunophysiology as well as that of Digestion and Reproduction.

• The colostrum is the first milk produced 5‑7 days after parturition and it is the first food taken by the newborn calf.

• Regarding its composition it is more similar to the blood rather than the milk. It consists of nutrients and a great variety of biologically active substances including immune components and growth factors. The constitution of the colostrum means that it is essential for the newborn and it has great potential as a product in the human nutrition and pharmacy markets. (Penchev Georgiev, I., 2008).

Part 1: The Colostral Components

• The exact composition of the colostrum may vary according to the stage of lactation, or due to pathological conditions (e.g. mastitis might be responsible for the presence of maternal epithelial cells (MEC) originating from the mammary gland of the mother) (K. Stelwagen et al 2008)

• In the attached file you will find a list of the most important colostral components, the importance of which will be explained later in respect to the function of the colostrum to the newborn as well as its application for the treatment of certain diseases of the gastrointestinal path.

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Part 2: Key Learnings on the importance and the physiology of colostrum uptake by the calf

Why is the colostrum of special importance to the new born calf ?

• The calf is born "undefended"

• The bovine placenta does not allow the transfer of immune material from the cow to the calf . Therefore the newborn is very sensitive to infections. This is compensated by the intake of colostrum, which with its high immunoglobin concentration (see part 1) is responsible for establishing passive immunity to the newborn.

Intestinal absorption of colostral immunoglobins

• As we already know, food is degraded in the digestive tract and digestion products are absorbed into the tissues . Suprisingly however, at birth and for a limited period of time thereafter, the secretion of digestive enzymes in the gastrointestinal tract of the calf declines in order to allow macromolecules (such as IgG) to «escape» digestion. This is particularly important for the absorption of colostral immunoglobulins, which would otherwise be digested and thus inactivated.
• The absorption of the colostral immunoglobins at the intestine follows a nonspecific (not receptor mediated) pathway. Macromolecules are taken into the intestinal absorptive cells (enterocytes) by the formation of tubules at the base of the apical microvilli. These tubules ‘pinch off’ in the cell to form small vesicles which transport the colostral immunoglobins to the basolateral membrane and release their contents at the extracellular space. From there the macromolecules can be taken into the circulation.
• This special type of absorption only occurs in the jejunum. Macromolecules can also be taken up by ileal enterocytes, but are degraded by lysosomes within the cell. Furthermore the absorption that takes place in the gastrointestinal tract of the calf postnatally, unlike selective pinocytosis, which resembles the above mentioned process, is extensive. Therefore, there is little discrimination in the absorption of the different immunoglobulins.

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Timing of absorption

• The process of macromolecular absorption is initially high during the first suckling and then it declines gradually. Finally intestinal closure occurs and intact macromolecules can no longer be absorbed. The intestinal closure is a continual, gradual process that starts immediately after birth and proceeds until macromolecules (including immunoglobulins) can no longer pass from the intestinal lumen, through the intestinal cell and into the neonate's vascular system. The direct absorption of intact macromolecules across the intestinal epithelium and into the neonatal circulation lasts for approximately 24 hours after parturition .

Growth factors

• Recently it has been shown that among the constituents of the bovine colostrum, there is a great variety of numerous growth factors and hormones, including insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II), epidermal growth factor (EGF), transforming growth factor (TGF), insulin, cortisol, relaxin and thyroxine, which are involved in the normal growth of the newborn. Most notably IGF-I and II, have been shown to be of particular importance to the development of the calves, as well as to the maturation of their digestive system, thus playing an important role in their future performance an adult cows.

Laxative effects

• Another interesting fact about the colostrum is its function as a natural laxative.
• As we have seen in the lectures, some of the substances found in the colostrum induce the discharge of the meconium.
• The meconium is a sticky, dark greenish brown mass, consisting of products of amnionic fluid digestion, gastrointestinal secretions, bile, and cellular debris. This mass accumulates in the intestines of the fetus prior to parturition. The meconium is normally excreted during the first hours of life. The inability to pass the meconium (meconium impaction) may be a function of delayed colostrum uptake and will have a great impact on the calf (severe abdominal pains).

Nutrients

• Last but not least we should not forget that the primary importance of the colostrum, apart from its role in establishing immunity, is to serve as a highly nutritional, easily digestible feed which provides the newborn with all the necessary proteins, minerals, vitamins etc.

Part 3: Brief Overview of Potential Applications of Bovine Colostrum in Gastrointestinal Diseases

• In addition to the already known natural beneficial effects of bovine colostrum (BC), in the newborn farm animals, a high number of studies are showing the applications of colostrum as a nutraceutical, due to its immunomodulatory properties for the treatment of a wide range of diseases. The early encouraging results are envisioning the standard use of colostrum in the near future, especially in the clinical management of gastrointestinal diseases. As stated before the BC nutrient profile and immunological composition is substantially different from the “mature” milk. In addition to the common nutrients found in milk such as proteins, carbohydrates, fats, macro and micronutrients, BC contains oligosaccharides, growth factors, antimicrobial compounds, and immune-regulating constituents, which are either not present or present in substantially lower concentrations in milk. Due to the fact that the colostral components that give its nutraceutical properties are nearly identical in structure and function among different species, it could be effectively used across species. (Pandey et al, 2011). The gastrointestinal (GI) tract is constantly under attack from acid, proteolytic enzymes and ingested noxious agents like bacteria, viruses, fungi and parasitic pathogens. These aggressions make infections of the digestive system, such as gastroenteritis, a common occurrence. As generally described next, some of these illnesses can be treated or, in certain cases even prevented, due to the action of the special constituents present in colostrum.

  Colostral immunoglobins (Ig), when administered orally are not absorbed into the blood stream, in the case of animals older than 36 to 48h, but within the GI tract of animals of all ages they can be very effective against pathological organisms. By binding and agglutinating the invading organisms, Ig facilitates their removal. They also prevent the pathogens from binding to the intestinal surface inhibiting in this way an important step of the infection process (Pandey et al, 2011). Although the Ig concentration in BC is enough to neutralize enteric pathogens, some researchers consider that the amount of Ig naturally available in the BC is too low to afford protection against some specific infectious organisms (Kelly, 2003). One of the ways to overcome this limitation is through the use of “hyperimmune bovine colostrum” (HBC). Although different infections may require different immunization technics (organisms used, inoculation route, frequency of administration), generally, the production of HBC consists of exposing pregnant cows to specific immunological challenges with the aim of increasing specific Ig, which may not be present originally in BC or may exist in low concentration (Kelly, 2003). For example, in order to create HBC directed to the treatment of diarrheas originated by rotavirus, pregnant cows are exposed to this virus, and the colostrum collected from these cows will have higher concentrations of specific neutralizing Ig against it. Encouraging results have been observed in the treatment, or in some cases prevention, of infections caused by Cryptosporidiosis, Helicobacter pylori, Rotavirus and Shigella. A number of naturally occurring substances like growth factors, that are also present in the BC, have receptors throughout the intestinal tract. This receptors which are postulated to be mediators of the intestinal growth and development, are known to increase the cell mass of the intestine, influence the composition of absorptive surface and may be involved in the stimulation of wound healing (Pandey et al, 2011). For example the platelet-derived growth factor (PDGF), which is one of the many growth factors present in the colostrum, is a potent mitogen for fibroblasts and arterial smooth muscle cells and when administered orally to animals have been shown to facilitate ulcer healing (Playford et al, 2000). Iron binding glycoproteins, lactoferrin and transferrin by binding the free iron molecules present in the gut and by moving the iron in the blood stream can slow pathogen growth. Lactoferrin can act directly on the pathogens by destabilizing the coat membranes in Gram negative bacteria allowing the immune system to attack them more successfully. It can also act as a signal to stimulate the immune system by binding to receptors in the intestines and exhibit antiviral properties most likely by attaching to the virus preventing it to enter the cells (Pandey et al, 2011). In conclusion bovine colostrum can be of significant use in different animal species for enhancing cell mediated immune response. It can be given as a treatment against established infections or in conjunction with traditional treatments. There are occasional minor side effects reported, but do not result in the discontinuation of treatment (Kelly, 2003). In most of the studies there are no side effects reported associated to the administration of high quality colostrum, being the worst case scenario the no treatment effect, which can make it a safe and useful nutraceutical product.

References

1. 1. Kelly, G.S. (2003): Bovine Colostrums: A Review of Clinical Uses. Alternative Medicine Review 8: (4) 378-394.

3. 2. Pandey, N.N., Dar, A. A., Mondal, D.B., Nagaraja, L. (2011): Bovine colostrum: A veterinary nutraceutical. Journal of Veterinary Medicine and Animal Health 3: (3) 31-35.

5. 3. Playford, R. J., Macdonald, C. E., Johnson, W. S. (2000): Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. The American Journal of Clinical Nutrition. 72: 5-14.

6. 4.John D. Arthington. (2001). Colostrum Management in Newborn Calves. Available: http://edis.ifas.ufl.edu/an110. Last accessed 18 oct 2012. 5.Brian Lang. (2008). Colostrum for the Dairy Calf. Available: http://www.omafra.gov.on.ca/english/livestock/veal/facts/08-001.htm. Last accessed 20 nov 2012. 6.Maude lebrun. (2010). colostrum et tranfert d immunité. Available: http://www.arsia.be/wp-content/uploads/2010/09/brochure-colostrum-v2-light.pdf. Last accessed 20 nov 2012.