Advances in bovine colostrum biology
Amrita Behera1, Atul Walunj2, Virendra Kumar Singh3
1- PhD Scholar, Indian Veterinary Research Institute, Uttar Pradesh
2- Assistant Professor, Rajiv Gandhi Institute of Veterinary Education and Research, Pondicherry
3- Assistant Professor, Navsari Agriculture University, Gujarat
INTRODUCTION
The underpinning of an immune-competent system for manifestation of a healthy well- being is often laid by the indispensible elixir of life, called ‘colostrum’. It seeks paramount importance not only in terms of catapulting juveniles’ immune status in combating pernicious life-threatening agents but also fosters and strengthens neonates’ essential nutritional requirements. Every single drop is precious as it encompasses an effective concoction of vital ingredients serving as a pre-requisite for salubrious productive life.
Colostrum is the first form of milk produced by the mammary glands of mammals immediately following the delivery of the new-born. It is a thin, yellowish, protein-rich fluid secreted at the time of parturition and precedes the production of true milk. It serves as the panacea during the fragile and wee hours of immune-compromised status of new-born as it consolidates and reinforces its defenses to counteract noxious elements.
With plenitude scores of function, the four main health benefits colostrum renders is: immune system modulation, gastro-intestinal function improvement, growth stimulation and anti-ageing effects. It boosts body’s natural defenses and also modulates immune function back to normal levels when it is “over-stimulated”. Therefore, rather than unilaterally increasing immunity, colostrum serves as an effective immune-modulator. It detoxifies body and strengthens gastro-intestinal functions by inhibiting harmful pathogens colonizing the gut while on other hand also promotes growth of beneficial bacterial colonies. With a range of growth factors such as ( EGF, TGF, IGF), it promotes bone density and also delays aging process.
As the age escalates, production of immunoglobulin is drastically reduced. Colostrum can restock some of its primeval aspects by promoting cellular growth. It also possess mild-laxative effect facilitating the passing of neonates first stool, called meconium. Owing to its myriad multitudinous health benefits, now bovine colostrum is exploited to serve as bioactive components in human nutrition.
NUTRITIONAL COMPOSITION
Colostrum has prolific and dynamic concentration of components in terms of its chemical composition. It serves as the amalgamation of carbohydrates lipids, proteins, immunoglobins, growth factors, nucleotides, nucleosides, minerals, vitamins and many more in concentrations appropriate enough to nourish the early crucial stages of calf development by rendering immuno dynamic and sustenance functions. In relation to lactose, a sugar composed of glucose and galactose, the concentration is quite low in colostrum and usually follows an inverse equation to other constituents such as fats, protein and ash. The presence of lactose demands for an higher accountability as it is responsible for 50% of milk’s osmotic pressure and its production enhances the mobility of water from mammary epithelial cells’ cytoplasmic compartment to secretory vescicles and finally into milk. This influx of water so resulted, regulates the volume as well as the concentration of casein. As it serves as an ace osmoregulator, absence of it can result in extremely viscous milk.
The concentration of oligosaccharides in colostrum accounts to be approximately 0.7 -1.2 gm/L of which a major fraction is acidic. Oligosaccharides can be categorized into two broad classes: neutral and acidic. Neutral oligosaccharides contain carbohydrate with no charged residue whereas acidic ones contain one or more negatively charged residue of N-acetyl neuraminic acid. In addition, it also serves as the most prolific bioactive component of milk in rendering protection against pathogens as it acts as the competitive inhibitor for the binding sites on epithelial surface of the intestine. It also holds importance in facilitating the growth of beneficial microflora in colon.
Compared to the human milk, the level of oligosaccharides is quite low in bovine milk but due to the similarity of its chemical structure, bovine oligosachharides are now used in milk products as bioactive components in human nutrition. Casein being the chief milk protein accounts for a slightly higher concentration in colostrum than in milk. It is amorphous white solid, tasteless, odourless in pure form and is related to the family of phosphoproteins. As suggested by several reports, the αs and κ- casein fractions of colostrum follows a variation in trend in terms of its concentration and stages post-partum as early post-partum milk contains reduced concentration of αs-casein and elevated κ-casein fractions whereas the fraction reverses with elapse in time.
Another major protein which holds utmost importance in colostrum is the immunoglobulins as it accounts for about 75-80% of total protein.
Concentration of immunoglobulins in colostrum and normal milk
Immunoglobulins Colostrum Normal milk(gm/L)
IgG1 52.0-87.0 0.31-0.40
IgG2 1.60-2.10 0.03-0.08
IgM 3.70-6.10 0.03-0.06
IgD 3.20-6.20 0.04-0.06
During early post-partum, as animal undergoes stress, they enter a state of negative energy balance. During this state, mobilization of adipose tissue fatty acids and incorporation of these fatty acids into milk fat occurs. Hence, the level of long- chain fatty acids is generally high in colostrum than in milk.
The non-protein nitrogen fraction of the milk comprises of nucleotides and nucleosides. The physiological capacity of these compounds in milk is given by the potentially available nucleosides. They serve as major bioactive substances regulating various body functions such as enhancement of immune function, nucleic acid synthesis, metabolism of fatty acids and gastrointestinal tract repair. Colostrum is rich in nucleotides with pyrimidine levels generally high as compared to purine nucleotides.
Colostrum serves as the reservoir inhabiting several family of enzymes such as antioxidant enzyme, proteinases, lipases, esterases and many more. The best example of antioxidant enzyme is the lactoperoxidase which is a basic glycoprotein containing a heme group with Fe3+. It catalyses the oxidation of thiocyanate (SCN-) in the presence of H2O2 producing a toxic intermediary oxidation product. This product causes the oxidation of sulfhydryl groups in protein and inhibits bacterial metabolism being toxic to both Gram positive and Gram negative bacteria. Its concentration in bovine colostrum is 11-45 mg/L.
Lactoferrin, another glycoprotein is an 80 KDa iron-binding protein is present in colostrum and is significantly related in conferring antimicrobial action. It is also involved in iron uptake in intestine and induces immune responses by activating phagocytes with its receptors present on intestinal tissues, macrophages, monocytes, lymphocytes, neutrophils and platelets. The antimicrobial action is rendered by inhibiting the growth of several microbes including Escherichia coli, Salmonella typhimurium, Shigella dyssenterie, Listeria monocytogenes, Streptococcus mutans and Bacillus subtilis with its N-terminal peptides being giarcidicidal against Giardia lamblia. Based on its capacity to bind iron, an essential factor for the growth of bacteria, it furnishes its action against microbes.
The principal indigenous proteinase in colostrum is the plasmin having affinity for lysine and arginine residues. It cleaves Lys-X and Arg-X bonds. Plasmin is secreted as plasminogen and is activated in blood and milk. With its optimal activity around 7.5 pH at 37°C, it is the predominant proteinase in colostrum and usually has 10 fold higher concentration in colostrum than in milk. The lipolytic activity of colostrum is maintained through lipases and esterases.
Extensive proteomic investigations were undertaken to understand the comparative framework of colostrum proteome and mature milk proteome. Bioinformatic tools revealed a clear and differentiating presence of 50 protein polypeptides and oligopeptides in cellular fraction of colostrums. Besides 13 different proteins are presented exclusively in mature milk with 99 different proteins found common in both bovine colostrum and milk. Having this novel information, it is possible that these differenting polypeptides of colostrum will aid in functionally defining the bovine colostrum from mature milk. An enormous rich addition of vitamins and minerals like Vit-A, Vit-E and Vit-D in colostrum not only escalates its nourishment capacity but also makes it an essential elixir for sustenance.
Minerals in milk is either present as ions in solution or as colloidal compounds complexed with caseins. It has an ideal proportion of variety of minerals such as zinc, citrates, phosphates, chlorides of K+, Na+, Mg2+ and Ca2+ and also some portions are associated together in form of salts such as Ca phosphate. While milk level of all minerals decreases with increase in lactation age, zinc is believed to decrease in fastest rate.
A mechanism involving low-density lipoproteins is associated with the transfer of vitamins into colostrum. The concentration of Vit-E in colostrum is high ranging from 60-1040 μg /100g. As α-tocopherol do not cross placenta in appreciable amounts, hence there is a limited reservoir of it once the calf is born. To compensate that, calves depend on the major supply of Vit-E through colostrum. Calves also do not synthesize endogenous Vit-C until they attain an age of 3 weeks, till this period they sustain on Vit-C obtained through colostrum. It is an ideal immunomodulant and helps in the maintenance of a natural barrier against infection. It facilitates growth, development as well as survival by augmenting antibody production, complement levels, stimulating leucocytes for rendering phagocytic actions and also enhancing synthesis of interferons.
Since parturient cows with their unique placental histoarchitechure are characterized by independent maternal and fetal blood supply, the transmission of immunologic factors from the dam to the fetus is restricted in utero. Thereby making newborn calves immunologically vulnerable. Also at birth the neonatal calves unlike adult bovines have diminutive capacity to mount successful immune response against invading environmental pathogens which then puts them at high risk for calfhood diseases. Subsequently the calves are immunologically incompetent to maintain active state of immunosurveillance. It takes at least 5-8 months for those critical immune factors to become mature enough and be completely functional.
Therefore diseases in calves and heifers can retard them, from achieving their genetic potential as productive adult cows. Recurring financial loss associated with disease treatment along with lost production can hamper long term dairy farm economy. Moreover, indiscriminate use of antibiotics for disease treatment and prevention faces increasing surveillance in all livestock species. A comprehensive understanding of neonatal immune-physiology and the symptomatic changes registered during an immune response may provide better insights into possible means of disease intervention. Simultaneously one of the prime factors that strongly impacts bovine neonatal immune function is the initial feeding of colostrums. But the effect and extent of dam’s environmental influence in the calf’s development does not end at parturition but is rather continuous throughout the 1st week of life as consequential effect of immunofunctional and growth promoting factors in colostrum, a concept recently described as lactocrine hypothesis.
As low titer of antibodies leads to increased morbidity and mortality rates in newborn calf, providing them with immunoglobulins, primarily IgG has been the foremost reason colostrum is fed. Post completion of gestational term, the calves are born with a unique property of transient nature; the ability to absorb or transfer immunoglobulins across the gut barrier, directly into the blood circulation thus providing protection against septicaemia. Chiefly IgG1 and IgG2 are two sub-classes of IgG found in the blood of the cow, wherein the udder traps and concentrates IgG1, but not IgG2. As a result, natural colostrum contains high levels of the IgG1. As ingested, IgG1 gains entry into peripheral circulation of calf following which, some of it is re-secreted back into the intestines and the lungs where it provides local immunity to prevent the two most common diseases of calves, diarrhoea and pneumonia for the first critical weeks of life.
Immunoglobulins are imperative in preventing infectious diseases, and this is the calf’s prime means of acquiring immunoprotection early in life. However, as critical hours passes by, the ability to absorb antibodies progressively decreases. Studies have shown that the efficiency of antibody migration across the gut barrier drops to about 50% by 6 hours and stops completely by 24 hours after birth. Colostrum must be fed as soon as possible after birth, ideally within an hour, and no later than 6 hours.
The amount of IgG in colostrum can be quantified, and good quality colostrum contains more than 50g/L of IgG. Calves should receive at least 100g IgG but feeding of 150-200g IgG is recommended for achieving higher serum antibody titer. With respect to the risk of transmitting pathogenic agents to the neonate calf, some studies suggest that high bacterial counts in colostrum can reduce transfer efficiency of colostral immunoglobulins and thus weaken calf’s immune response. Proper hygiene is prerequisite in minimizing contamination of colostrum during collection, storage and feeding. Bacteria count should be less than 100,000 CFU/mL and colostrum should be free of extraneous dirt, blood, and mastitis. If the fed colostrum to the calves is of poor quality (low antibody titer coupled with high bacterial count) significant proportion of future productive herd will be susceptible to environmental infections. Thus colostrum management for effective herd biosecurity requires that the newborns have optimum levels of protective immunity to the specific pathogens in the environment. Most common causes of calf morbidity and mortality during the first 3 weeks of life are pneumonia and diarrhoea. Thus feeding high-quality colostrum will positively influence successful transition of a newborn calf to an effective productive cow.
But since the quality of colostrum depends on the breed of cow, parity etc, the real concern lies in the vacillating nutritional and immunological quality of bovine colostrum and the impact of this variability on calf health and management.
Apart from maternally derived immunoglobins, colostrum also contains large no of maternally derived immune cells, which then post ingestion actively contribute to the immunoprotection of calf health. The cellular fraction of colostrum constitutes macrophages, epithelial cells, polymorphonuclear cells, B and T lymphocytes in varying proportions; amongst which colostral macrophages constitute the predominant cell type in normal bovine colostrum. Although bovine colostrum contains approximately 106 leucocytes/ml, variation may be observed with respect to age, breed, immune and health status of cows at the individual level.
Following timely colostrum ingestion, colostral immune cells infiltrate the permeable neonatal gut barrier and enter the systemic blood circulation. Thus inducing a transient state of systemic cell mediated immunity. Moreover these colostral immune cells which have already processed foreign antigen will facilitate the induction of immune response against those processed foreign antigens that might not otherwise be induced because of antigen capture and inactivation by IgA in calf body. Concurrent to above facts, experiments have concluded that blood lymphocyte count in neonatal calves increased dramatically between 6-12 hr after ingestion of colostrum in contrast to all those calves deprived of colostrum. Thus, passive transfer of colostral leucocytes across the gut barrier facilitates in establishing active immune surveillance network in systemic and local tissues during the most critical hours of life.
To facilitate immunocompetency led by colostral leucocytes, they must undergo some major structure-functional changes under the influence of mammary colostral environment during colostrogenesis, thus facilitating their entry into systemic circulation of the neonate, post colostrum feeding. With subsequent loss of certain cell surface receptors (L-selectin) as one such structural modulation, there is simultaneous expression and regulation of surface markers that will aid the penetration of these cells across gut barrier and into systemic circulation of newborn calves and promote memory phenotype development. Moreover this physiological gut permeability is dam-newborn specific and that another dam’s colostral immune cells cannot migrate across foster newborns gut barrier leading to a sub immunoprotection of neonate.
Available literature suggests that bovine colostrum can be used not only in prevention but also to overcome adverse effects during chemotherapy. Sick individuals consuming bovine colostrum based products can regain their health status faster and maintain body weight.
Besides, bioactive components in bovine colostrum can successfully inhibit helicobacter pylori pathogenesis responsible for gut ailment. Two components of bovine colostrum played a vital role in reducing the negative impact of the disease. The first is lactoferrin which not only obliterates H. Pylori but simultaneously increases bacterial susceptibility to the antibiotic therapy while boosting immunity. The second immune-modulating component is lysozyme which together with lactoferrin showed antibacterial responses against such pathogenic microorganism. Moreover lactoferrin inhibits bacterial biofilms development by binding free iron essential for bacterial growth.
Numerous genetic, environmental, and immunological factors may play a role in the onset of gastrointestinal tract disorders affecting millions worldwide. One of which is Inflammatory bowel diseases (IBD) are a group of chronic recurrent inflammatory conditions. In human population, Crohn’s disease and Ulcerative Colitis are considered the most dangerous conditions included in IBD. Ongoing Studies on mice has clearly validated that bovine colostrum has the potential to modulate the immunological response as well as the severity of the intestinal inflammatory reaction modulating TLR4 and cytokine expression, reducing BW loss,and finally decreasing the clinical signs of colitis.
Failure of systemic immune system leads to rapid development of many immunocompromised diseases such as cancer, AIDS in human with no age led barrier. In recent past, the novel approach of bovine colostrum based immunotherapy has become an appealing strategy for the treatment of cancer and other such immunosuppressive diseases. Leading phagocytic cells such as macrophages are a principal arm of the cellular immune system within the body. Simultaneously, overall enhancement in macrophage functions is observed under stimulation of macrophage activator, endogenously found in blood. Thus MAF has been found to offer distinct health benefits. Comprehensive research on clinical efficiency of colostrum derived MAF is currently been looked upon as the next-generation substrate for MAF based immunotherapies.
This alternative bovine colostral MAF has some unique lead over the conventional serum derived MAF, that it can be administered orally because of its food based origin, instead of administering by invasive injection. Moreover, researchers have concluded that colostral MAF can be a novel immune therapeutic against autoimmune diseases, if modified colostrum MAF can be used to suppress the production of inflammatory cytokine. Therefore, bovine colostral MAF is a promising novel macrophage activator for distinct immunotherapies. The use of neutraceutical properties of bovine colostrum in human food market is gaining worldwide popularity
COLOSTRININ
Unique chemistry of proline rich peptides renders them with a potent bioactivity. PRPs have been reported to possess bioactivities ranging from antimicrobial action to prevention of neurodegenerative disorders. Since that, in many ways, it is not surprising that proline-rich peptides are found in bovine colostrum. One such colostrum related PRP is colostrinin whose potent immunomodulatory activity promises extensive use of colostrinin based next generation therapeutics in neurodegenerative disorders especially Alzheimer’s disease. Moreover Colostrinin through its antimutagenic properties also prevents malignant melanoma and squamous cell carcinomas by decreasing UVA and UVB radiation induced mutation frequency. These damaging radiations are a natural part of sunlight. This intervention is brought by decreasing intracellular levels of ROS and so preventing DNA damage and by increasing the efficiency of natural DNA repair mechanisms.
Moreover recent reports on colostrinin studies have also validated to work as potent B cell-trophic mitogen. Another such proline rich peptide from which a subunit isolated named NP-POL peptide presents its potential regulatory based mechanism of action in regulating the survival of nerve cells treated with neurotoxic 6-hydroxydopamine and its prospective use as a therapeutics in the treatment of Parkinson’s disease. Also, due to its composition in Tumor necrosis factor-alpha (noted as TNF-α), the colostrum reduced pain in inflammation or swelling. Another very important protein found in colostrum interleukin-1ra (IL-1ra) is reduces the pain, swelling and inflammation.
Advance bioengineering techniques applied in animal breeding can produce novel animals that yield value added colostrum with a higher concentration of immunoglobulin and range of bioactive peptides in colostrums, thus making it superfood!
