Colostrum, or first milk, is the first form of milk produced by the mammary glands of humans and other mammals immediately following delivery of the newborn. [1] It may be called beestings when referring to the first milk of a cow or similar animal. [2] Most species will begin to generate colostrum just prior to giving birth. Colostrum has an especially high amount of bioactive compounds compared to mature milk to give the newborn the best possible start to life. Specifically, colostrum contains antibodies to protect the newborn against disease and infection, and immune and growth factors and other bioactives that help to activate a newborn's immune system, jumpstart gut function, and seed a healthy gut microbiome in the first few days of life. The bioactives found in colostrum are essential for a newborn's health, growth and vitality. [1] Colostrum strengthens a baby's immune system and is filled with white blood cells to protect it from infection.
At birth, the surroundings of the newborn mammal change from the relatively sterile environment in the mother's uterus, with a constant nutrient supply via the placenta, to the microbe-rich environment outside, with irregular oral intake of complex milk nutrients through the gastrointestinal tract. [3] This transition puts high demands on the gastrointestinal tract of the neonate, as the gut plays an important part in both the digestive system and the immune system. [4] Colostrum has evolved to care for highly sensitive mammalian neonates and contributes significantly to initial immunological defense as well as to the growth, development, and maturation of the neonate's gastrointestinal tract by providing key nutrients and bioactive factors. Bovine colostrum powder is rich in protein and low in sugar and fat. [5] [6] Bovine colostrum can also be used for a range of conditions in humans, and can boost a neonate's immunity. [7]
Colostrum also has a mild laxative effect, encouraging the passing of a baby's first stool, which is called meconium. [8] This clears excess bilirubin, a waste-product of dead red blood cells which is produced in large quantities at birth due to blood volume reduction[ citation needed ] from the infant's body and which is responsible for jaundice.
Newborns have very immature and small digestive systems, and colostrum delivers its bioactives in a very concentrated low-volume form. Colostrum is known to contain immune cells (as lymphocytes) [9] [10] and many antibodies such as IgA, IgG, and IgM. These are some of the components of the adaptive immune system. Other immune components of colostrum include the major components of the innate immune system, such as lactoferrin, [11] lysozyme, [12] lactoperoxidase, [13] complement, [14] and proline-rich polypeptides (PRP). [15] A number of cytokines (small messenger peptides that control the functioning of the immune system) are found in colostrum as well, [16] including interleukins, [16] tumor necrosis factor, [17] chemokines, [18] and others.
Colostrum also contains a number of growth factors, such as insulin-like growth factors I (IGF-1), [19] and II, [20] transforming growth factors alpha, [21] beta 1 and beta 2, [22] [23] fibroblast growth factors, [24] epidermal growth factor, [25] granulocyte-macrophage-stimulating growth factor, [26] platelet-derived growth factor, [26] vascular endothelial growth factor, [27] and colony-stimulating factor-1. [28]
Colostrum, which is produced for the first two to four days after childbirth, enhances immunity [29] [30] and is believed to have anti-inflammatory properties. [31] It is suggested infants fed with human colostrum have lower incidence of gastrointestinal infections. [32]
While it has long been understood that the colostrum a mother produces is vital to a newborn's health in the first few days of life, research has shown that bovine (cow) colostrum and its components can continue to support important biological activities when given to more mature children and adults, so that the benefits of colostrum can extend well beyond the neonatal period of development. [33]
Bovine colostrum and human colostrum are highly similar in their makeup, both containing many of the same antibodies, immune and growth factors, and other nutrients. [34] Because they share so many of the same components, the way they work in the body is also highly similar. The benefit of bovine colostrum for human health has been studied in many areas including:
There is also research suggesting that a large proportion of colostrum is not fit for human consumption "due to tremendous bacterial loads". Salmonella was also detected in 15% of unpasteurised samples. [49] Pasteurisation reduces the bioactive proteins many of the benefits rely upon, however. [50]
Colostrum is crucial for newborn farm animals. They receive no passive transfer of immunity via the placenta before birth, so any antibodies that they need have to be ingested (unless supplied by injection or other artificial means). The ingested antibodies are absorbed from the intestine of the neonate. [51] [52] [53] [54] [55] The newborn animal must receive colostrum within 6 hours of being born for maximal absorption of colostral antibodies to occur. Recent studies indicate that colostrum should be fed to bovines within the first thirty minutes to maximize IgG absorption rates. [56]
The role of colostrum for newborn animals is to provide nutrition, and essential protection against infection while the immune and digestive systems are developing and maturing. Bovine colostrum provides macro- and micro-nutrients, as well as growth factors, cytokines, nucleosides, oligosaccharides, natural antimicrobials, antioxidants; and a range of immunoglobulins such as IgG, IgA, IgD, IgM and IgE. It is well established that minimal levels of IgG are essential to prevent failure of passive transfer. The iron-binding glycoproteins lactoferrin and transferrin in bovine colostrum assist in attacking pathogens by impacting their cell membrane and making them more susceptible to the immune systems attack by neutrophils. Cytokines present in bovine colostrum enhance B and T cell maturation and increase endogenous antibody production. They also play a major role in regulation of epithelial cell growth and development, proliferation, and restitution. Transfer factors enhance the activity of T cells. Other growth and immune factors such as IGF-1, IGF-2, FGF, EGF, TGF, PDGF, etc.
Bovine colostrum's components benefit the immune and digestive health of animals of all ages and species. Bovine colostrum's vast array of bioactive components collectively increase resistance to infection and disease caused by a wide range of pathogens including bacteria and viruses. The quality of the colostrum is essential in providing the essential benefits. Both contaminated early bovine colostrum at the farm level or late transition milk or milk are poor sources of the important colostral components necessary to maintain life and achieve and maintain healthy animal maturation and homoeostasis. Bovine colostrum also is beneficial in repairing or healing intestinal damage as well as increasing the absorption of nutrients from the GI tract. These properties and benefits are consistent among human and animal species.
The transition from fetal to neonatal and shift from maternal to environmental reliance requires an abrupt immunological change. In calves, for example, colostrum provides a significant benefit in neonatal intestine development. This includes villus area, circumference, height and height/crypt ratio. Colostrum is critically important to calves and foals in order to prevent failure of passive transfer and death. Calves, foals and piglets with low IgG levels have an increased risk of morbidity and mortality. Bovine colostrum can be used to reduce the duration and severity of infections so it can be a useful tool to include in the reduction of antibiotic use. Finally, another important and valuable benefit of colostrum is in the reduction in scours and increase in average daily weight gain all of which have a significant farmer and ultimately consumer benefit.
Much like in humans and production animals, companion animal survival in the newborn stage of life is largely dependent upon colostrum. Companion animal immune systems require several weeks to several months in order to fully develop. Maternal antibodies provide benefit for a relatively short period of time so a gap exists with immune sufficiency where an animal is at risk of infection. Like humans, companion animal immune response changes with age where early life and later in life have similarities. That is, an immune bias whereby the animal has less of an ability to fend off infections and greater prevalence of allergy at both ends of the age spectrum. Stress also affects a companion animal's immune system including changes in environment, diet, etc. Maintaining gut microbial balance is key to maintaining a healthy immune system as well as mucosal integrity, similar to humans. Bovine colostrum has been demonstrated to benefit companion animal immunity and digestive health.
Bovine colostrum plays a role in increasing Ig levels, increasing lymphocyte proliferation stimulating activity and increasing phagocytosis activity. These are supported by other components of colostrum which further enhance the activity of the immune response. The iron binding glycoproteins lactoferrin and transferrin in bovine colostrum assist in attacking pathogens by impacting their cell membrane and making them more susceptible to the immune systems attack by neutrophils. Cytokines present in bovine colostrum enhance B and T cell maturation and increase endogenous antibody production. They also play a major role in regulation of epithelial cell growth and development, proliferation, restitution. Transfer factors enhance the activity of T cells. Other growth and immune factors such as IGF-1, IGF-2, FGF, EGF, TGF, PDGF, etc. Colostrum contains glycomacropeptides which help to regulate appetite.
Bovine colostrum has been shown to enhance immune response in animal models including canine, feline and equine animals including maintaining a higher level of vaccine antibody response over time and for a longer period than the vaccine alone. Animals fed colostrum had a significantly higher local immune status resulting in higher IgA through GALT stimulation. Colostrum also plays a key role in reduction or prevention of diarrhea and reduction in respiratory illness.
Dairy cattle are naturally exposed to pathogens and produce immunoglobulins against them. These antibodies are present in the cow's bloodstream and in the colostrum. These immunoglobulins are specific to many human pathogens, including Escherichia coli, Cryptosporidium parvum, Shigella flexneri, Salmonella species, Staphylococcus species, [57] and rotavirus (which causes diarrhea in infants). Before the development of antibiotics, colostrum was the main source of immunoglobulins used to fight bacteria. In fact, when Albert Sabin made his first oral vaccine against polio, the immunoglobulin he used came from bovine colostrum. [58] When antibiotics began to appear, interest in colostrum waned, but, now that antibiotic-resistant strains of pathogens have developed, interest is once again returning to natural alternatives to antibiotics, namely, colostrum. [59]
Although bovine colostrum has been consumed by humans for centuries, [60] only in recent decades have we seen an increase in randomized clinical trials to support assertions of health benefits. It is probable that little absorption of intact growth factors and antibodies into the bloodstream occurs, due to digestion in the gastrointestinal tract. However, the presence of casein and other buffering proteins does allow growth factors and other bioactive molecules to pass into the lumen of the small intestine intact, where they can stimulate repair and inhibit microbes, working via local effects. [61] This provides a probable mechanism explaining reductions in gut permeability after colostrum administration in some published studies, [62] [63] [64] while another study found colostrum promising as treatment for distal colitis. [65] Evidence for the beneficial effect of colostrum on extra-gastrointestinal problems is less well developed, due in part to the limited number of randomised double-blind studies published, although a variety of possible uses have been suggested. [66] [67] [68]
The gut plays several important roles including acting as the main pathway for fluid, electrolyte and nutrient absorption while also acting as a barrier to toxic agents present in the gut lumen including acid, digestive enzymes and gut bacteria. It is also a major immunological defence mechanism, detecting natural commensals and triggering immune response when toxic microbes are present. Failure of homeostasis due to trauma, drugs and infectious microbes not only damages the gut but can lead to influx of damaging agents into the bloodstream. These mechanisms have relevance for multiple conditions affecting all areas of the world and socioeconomic groups such as ulcers, inflammation, and infectious diarrhea. [69] There is currently much interest in the potential value of colostrum for the prevention and treatment of these conditions as it is derived from natural sources and can influence damaging factors through multiple pathways including nutritional support, immunological intervention (through its immunoglobulin and other anti-microbial factors) and growth/healing factor constituents. [70] As pointed out by Kelly, inconsistency between results in some published studies may be due in part to variation in dose given and to the timing of the colostrum collection being tested (first milking versus pooled colostrum collected up to day 5 following calving). [71]
Some athletes have used colostrum in an attempt to improve their performance, [72] decrease recovery time, [45] and prevent sickness during peak performance levels. [73] [74] Supplementation with bovine colostrum, 20 grams per day (g/d), in combination with exercise training for eight weeks may increase bone-free lean body mass in active men and women. [72] [75]
Low IGF-1 levels may be associated with dementia in the very elderly, although causation has not been established. [76] Malnutrition can cause low levels of IGF-1, [77] as can obesity. [78] Supplementation with colostrum, which is rich in IGF-1, can be a useful part of a weight reduction program.[ citation needed ] Although IGF-1 is not absorbed intact by the body, some studies suggest it stimulates the production of IGF-1 when taken as a supplement [79] whereas others do not. [47]
Colostrum also has antioxidant components, such as lactoferrin [80] and hemopexin, which binds free heme in the body. [81]
The Isle of Man had a local delicacy called "Groosniuys", a pudding made with colostrum. [82] In Finland, a baked cheese called Leipäjuusto is traditionally made with either cow colostrum or reindeer milk.
A sweet cheese-like delicacy called 'Junnu' or 'Ginna' is made with colostrum in the south Indian states of Karnataka, Andhra Pradesh and Telangana. It is made with both cow and buffalo milk; in both cases it is the milk produced on the second day after giving birth which is considered best for making this pudding-like delicacy. Colostrum is in very high demand in these states, resulting in product adulteration. [83]
Hyperimmune colostrum is natural bovine colostrum collected from a population of cows immunized repeatedly with a specific pathogen. The colostrum is collected within 24 hours of the cow giving birth. Antibodies towards the specific pathogens or antigens that were used in the immunization are present in higher levels than in the population before treatment. Although some papers have been published stating that specific human pathogens were just as high as in hyperimmune colostrum, and natural colostrum nearly always had higher antibody titers than did the hyperimmune version. [57] Clinical trials [84] have shown that if the immunization is by surface antigens of the bacteria, the Bovine Colostrum Powder [85] can be used to make tablets capable of binding to the bacteria so that they are excreted in stools. This prevents the successful colonization of the gut, which would otherwise lead to bacteria releasing enterotoxigenic materials.
These small immune signaling peptides (PRPs) were independently discovered in colostrum and other sources, such as blood plasma, in the United States, [86] Czechoslovakia and Poland. [87] Hence they appear under various names in the literature, including Colostrinin, CLN, transfer factor and PRP. They function as signal transducing molecules that have the unique effect of modulating the immune system, turning it up when the body comes under attack from pathogens or other disease agents, and damping it when the danger is eliminated or neutralized. [88] At first thought to actually transfer immunity from one immune system to another, it now appears that PRPs simply stimulate cell-mediated immunity. [89]
A kitten is a juvenile cat. After being born, kittens display primary altriciality and are fully dependent on their mothers for survival. They normally do not open their eyes for seven to ten days. After about two weeks, kittens develop quickly and begin to explore the world outside their nest. After a further three to four weeks, they begin to eat solid food and grow baby teeth. Domestic kittens are highly social animals and usually enjoy human companionship.
Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes.
Immunoglobulin A is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other types of antibody combined. In absolute terms, between three and five grams are secreted into the intestinal lumen each day. This represents up to 15% of total immunoglobulins produced throughout the body.
Immunoglobulin M (IgM) is the largest of several isotypes of antibodies that are produced by vertebrates. IgM is the first antibody to appear in the response to initial exposure to an antigen; causing it to also be called an acute phase antibody. In humans and other mammals that have been studied, plasmablasts in the spleen are the main source of specific IgM production.
Bovine somatotropin or bovine somatotrophin, or bovine growth hormone (BGH), is a peptide hormone produced by cows' pituitary glands. Like other hormones, it is produced in small quantities and is used in regulating metabolic processes. Scientists created a bacterium that produces the hormone somatotropin which is produced by the cow's body after giving birth and increases milk production by around 10 percent.
Breast milk or mother's milk is milk produced by the mammary glands in the breast of human females. Breast milk is the primary source of nutrition for newborn infants, comprising fats, proteins, carbohydrates, and a varying composition of minerals and vitamins. Breast milk also contains substances that help protect an infant against infection and inflammation, such as symbiotic bacteria and other microorganisms and immunoglobulin A, whilst also contributing to the healthy development of the infant's immune system and gut microbiome.
Transfer factors are essentially small immune messenger molecules that are produced by all higher organisms. Transfer factors were originally described as immune molecules that are derived from blood or spleen cells that cause antigen-specific cell-mediated immunity, primarily delayed hypersensitivity and the production of lymphokines, as well as binding to the antigens themselves. They have a molecular weight of approximately 5000 daltons and are composed entirely of amino acids. Transfer factors were discovered by Henry Sherwood Lawrence in 1954.
Microfold cells are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are known to initiate mucosal immunity responses on the apical membrane of the M cells and allow for transport of microbes and particles across the epithelial cell layer from the gut lumen to the lamina propria where interactions with immune cells can take place.
In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.
Infant feeding is the practice of feeding infants. Breast milk provides the best nutrition when compared to infant formula. Infants are usually introduced to solid foods at around four to six months of age.
Late preterm infants are infants born at a gestational age between 34+0⁄7 weeks and 36+6⁄7 weeks. They have higher morbidity and mortality rates than term infants due to their relative physiologic and metabolic immaturity, even though they are often the size and weight of some term infants. "Late preterm" has replaced "near term" to describe this group of infants, since near term incorrectly implies that these infants are "almost term" and only require routine neonatal care.
Serum-derived bovine immunoglobulin/protein isolate (SBI) is a medical food product derived from bovine serum obtained from adult cows in the United States. It is sold under the name EnteraGam.
Human milk oligosaccharides (HMOs), also known as human milk glycans, are short polymers of simple sugars that can be found in high concentrations in human breast milk. Human milk oligosaccharides promote the development of the immune system, can reduce the risk of pathogen infections and improve brain development and cognition. The HMO profile of human breast milk shapes the gut microbiota of the infant by selectively stimulating bifidobacteria and other bacteria.
Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.
Milk fat globule membrane (MFGM) is a complex and unique structure composed primarily of lipids and proteins that surrounds milk fat globule secreted from the milk producing cells of humans and other mammals. It is a source of multiple bioactive compounds, including phospholipids, glycolipids, glycoproteins, and carbohydrates that have important functional roles within the brain and gut.
The human milk microbiota, also known as human milk probiotics (HMP), encompasses the microbiota–the community of microorganisms–present within the human mammary glands and breast milk. Contrary to the traditional belief that human breast milk is sterile, advancements in both microbial culture and culture-independent methods have confirmed that human milk harbors diverse communities of bacteria. These communities are distinct in composition from other microbial populations found within the human body which constitute the human microbiome.
Human milk immunity is the protection provided to the immune system of an infant via the biologically active components in human milk. Human milk was previously thought to only provide passive immunity primarily through Secretory IgA, but advances in technology have led to the identification of various immune-modulating components. Human milk constituents provide nutrition and protect the immunologically naive infant as well as regulate the infant's own immune development and growth.
Milk immunity is the protection provided to immune system of an infant via the biologically active components in milk, typically provided by the infant's mother.
Breastmilk medicine refers to the non-nutritional usage of human breast milk (HBM) as a medicine or therapy to cure diseases. Breastmilk is perceived as an important food that provides essential nutrition to infants. It also provides protection in terms of immunity by direct transfer of antibodies from mothers to infants. The immunity developed via this mean protects infants from diseases such as respiratory diseases, middle ear infections, and gastrointestinal diseases. HBM can also produce lifelong positive therapeutic effects on a number of chronic diseases, including diabetes mellitus, obesity, hyperlipidemia, hypertension, cardiovascular diseases, autoimmunity, and asthma.
Breast milk-mediated drug delivery refers to the use of breast milk to transport a pharmaceutical compound, protein, or other treatment to achieve a desired effect. Delivery of these substances via milk provides an oral alternative for transport of a compound to the gut, specifically in infants. Breast milk-mediated drug delivery provides a way for pharmaceuticals and proteins to travel through the gastrointestinal system of an infant while minimizing the potential for irritation within gastrointestinal tissue.