Nutritional Parameters in Colostrum of Different Mammalian Species

Abstract

Colostrum (or first milk) is the food produced by all the mothers in all specific mammalian species, ruminants, monogastric and marine mammalians for their newborns during the first 24–48 h post-partum. Colostrum provides to the neonate all essential nutrients necessary for the first week of life, but the effect of colostrum shows a long-term effect not limited to these first days. Colostrum is considered to be a safe and essential food for human consumption. Some young children can show at the beginning of their colostrum-based diet some side effects, such as nausea and flatulence, but they disappear quickly. In human colostrum, the immunoglobulins and lactoferrin determined show the ability to create natural immunity in newborns, reducing greatly the mortality rate in children. Recent studies suggest that bovine colostrum (BC) may be an interesting nutraceutical food, due to its ability in preventing and/or mitigating several diseases in newborns and adults. This review aims to show the nutraceutical and functional properties of colostrum produced by several mammalian species, describing the different colostrum bio-active molecules and reporting the clinical trials aimed to determine colostrum nutraceutical and therapeutic characteristics in human nutrition.

1. Introduction

Human milk (HM) is constantly changing, according to the child’s age, in order to meet the feeding requirements of the infant’s growth and also to create proper immune system development and modulation [1].

Colostrum chemical composition differs significantly in nutrient content, depending firstly on genetic characteristics, such as animal species and breed, and secondly, according to the farm feeding management [2]. Colostrum is the secretion of the mammary gland produced in the first 48 h after parturition. The nutraceutical components of colostrum are mainly represented by immune and growth factors, but other molecules are also very important for a complete evaluation of colostrum quality parameters [3]. The laxative effect of colostrum on newborn babies is one of the most important actions, due to its crucial help in meconium evacuation (first stool), together with its help in eliminating the excess of bilirubin, preventing icterus [4]. The presence of immunoproteins in colostrum composition represents the main cause of infants’ protection against infections [5].

When natural mothers breastfeeding is not possible or it is not adequate to fulfill the baby’s feeding requirements, children are fed using milk formulas, specific foods produced as a replacer of both mother’s colostrum and/or milk. Formulas must provide specific nutrient content and are mainly prepared using different kinds and particularly different total amounts of cow’s milk proteins [6]. Milk formulas are classified in the following grid:

• Stage 1—infant formulas (0–6 months of age);

• Stage 2—follow-up formulas (6–12 months of age);

• Stage 3—toddler formulas (above 12 months of age),

to provide the nutrients necessary for the different stages of children’s development. Breastfeeding shows several other benefits for the children compared to the use of infant formulas, such as better brain development, stronger protection against infections, and also a good prevention of obesity [7]. Breastfeeding is normally recommended for at least the first 6 months of the infant’s life, and later, it should be continued for as long as possible together with the introduction of new foods in the infant’s diet [8].

Since colostrum is the first food for the neonate in all mammalian species and determines the initial postnatal substrate supply during the exclusive breastfeeding period, it deserves special investigation. This review describes the data available about colostrum produced by different mammals, comparing human colostrum with that produced by other domesticated mammalian species.

2. Human Milk

HM is the best food for feeding children, surely it is the best choice for achieving the feeding requirements for all neonates [9]. HM chemical composition is influenced by several parameters, such as the mother’s age, mother’s lactation stage, mother’s body mass index, parity number, and mother’s diet [10].

Mature HM is a complex biofluid that contains 1% protein, 4% fat, 7% carbohydrates, and 88% water, the protein concentration is high in the colostrum (around 14–15 g/L) but then decreases rapidly in mature HM reaching the average value of 7–8 g/L. Casein and whey proteins are the most abundant proteins in HM; however, it is known that this milk has about 1700 different proteins [11]. Regarding carbohydrates, lactose concentration is higher in mature HM (around 68.0 g/L), whereas in the colostrum its average concentration is 56.0 g/L [11]. In addition, HM contains vitamins, hormones, immunological factors, enzymes, and coenzymatic factors. Newborns show an immature immune system; therefore, the colostrum immunological properties are very important. Colostrum is an important source of Immunoglobulin A (IgA), Immunoglobulin G (IgG), and Immunoglobulin M (IgM). Milk IgA is different from that one determined in the plasma because it is a dimer with a J chain protein and a secretory component named SIgA (secretory IgA), resistant to intestine proteolytic digestion. SIgA concentration in the colostrum (5.4 g/L) is significantly higher compared to the value determined (1.3 g/L) in mature HM [11]. Lactoferrin is a glycoprotein showing antimicrobial and antiviral effects; Lactoferrin content is higher in the colostrum (5 g/L) compared to the value determined in mature HM (1.4 g/L). The immunological properties of HM are also influenced by a complex array of about 200 oligosaccharides playing an essential role in the development of the newborn microbiome. In colostrum, the concentration of these oligosaccharides is around 20–25 g/L, then decreases during lactation [12].

The human colostrum fat profile is characterized by high percentages of Polyunsaturated Fatty Acids (PUFA); in fact, PUFA content in colostrum tends to be at least twice that of PUFA content determined in mature milk [13]. Fat levels in colostrum are not high, showing values between 20 and 30 g/L [14] compared to the mean fat content of mature HM, which has been determined to be close to 40 g/L [15]. The high colostrum PUFA content can supply the low-fat colostrum content, providing nutritional benefits to the new-born, such as a strong bioactive effect on cell growth and function, the formation of eicosanoids, and the regulation of the cardiovascular system, immune system, and several other physiological functions [16].

3. Comparison between the Nutritional Properties of Human, Cow, Donkey, Buffalo, Goat, and Donkey Colostrum

3.1. Human Colostrum

Health benefits provided by Human Colostrum (HC) were discovered several years ago [17]; the gastrointestinal system in newborns is small and immature, and HC is the only food able to provide the required nutrients at the right adequate levels.

Compared to mature HM, HC in fact is rich in bioactive compounds containing immune and growth factors useful for the newborn protection against infectious diseases and also able to guarantee in the first 24 h of the newborn life gut microbiome healthy growth. In fact, thanks to prebiotic action, HC stimulates the immune system of the newborn, thus compensating for the immunological lack that characterizes preterm infants [18,19]. Civra and co-workers [18] found that HC possesses intrinsic antiviral activity against rotavirus and respiratory syncytial virus and that the extracellular vesicles (EVs) give a great contribution to the overall protective effect. The EVs include exosomes and microvesicles with a size ranging from 50 to 200 nm, which are released by several tissues including HM, and structurally are characterized by a lipid bilayer that encloses several molecules such as signaling proteins, mRNA, miRNA, and enzymes. EVs are taken up by other cells where they release the content of their molecules that exert their different role (intercellular signaling, immune response, viral replication, neuronal function, and tissue regeneration) [18].

HC plays an important role in newborns, due to its laxative effect, helping the baby in the passage of the initial stools called meconium, and also eliminating the excess of bilirubin from the baby’s intestine, preventing jaundice [19,20]. Antibodies in colostrum not only protect neonates against infectious diseases [21] but also provide passive immunity and growth factors for gastrointestinal development [22]. Values reported in Table 1 clearly show that lactose content in bovine colostrum (BC) is lower compared to HC and goat colostrum [23].

HC is considered a safe food for a large part of the human population; sometimes, side effects such as nausea and flatulence may appear in the first 48 h, then these symptoms decline after the second day. HC consumption must only be avoided for consumers showing milk allergies, intolerance to milk-based products, or people showing galactosemia [26].

Total protein can be considered the sum of caseins and whey proteins, with both components showing nutritional and bioactive properties [27]. Casein is the most represented phosphoprotein in dairy cows’ milk; the αs1-casein fraction is the predominant protein in bovine milk [28]. Human casein is characterized by peptides with opioid-type activity, affecting immune activity in children and helping the adsorption of other biologically active peptides [29]. Human casein consists of several sub-units, which form micelles with Ca⁺⁺ and PO₄⁻ causing the typical white color of milk [30]. The micelles in human casein are spherical colloidal particles, with an average size of 50 nm, containing around 94% protein and 6% non-protein species, mainly calcium and phosphate, called colloidal or micellar calcium phosphate (CCP or MCP) [30]. In several mammalian species, milk is supersaturated with calcium phosphate and the insoluble part (CCP) is present in the casein micelles; human milk has a small amount of CCP compared with ruminant species, and its micelles show a porous structure [30].

3.2. Bovine Colostrum

Bovine colostrum (BC) is a thick yellowish liquid containing a higher concentration of antibodies compared to mature milk [31]. Protein content in BC is higher compared to mature milk: protein fractions can be classified into two groups: whey proteins and caseins [32]. Caseins are the most abundant phosphoproteins in cow milk, being around 75% of total proteins [33]. Whey proteins include immunoglobulins, lactoferrin, α-lactalbumin, β-lactoglobulin, lactoperoxidase, and several growth factors [34]. α-lactalbumin is the most abundant peptide determined in BC whey proteins, being about 40% of total whey proteins, showing a high content of essential amino acids [35]. β-lactoglobulin contains 162 amino acids, being a good source of essential amino acids, but sometimes can be considered a major immunogen for people affected by cow milk protein allergies [36]. Lactose represents the most abundant carbohydrate in BC, being about 2.5%, a lower amount compared to mature bovine milk or human milk [37]. Lactose is a disaccharide formed by galactose and glucose; it plays an important role in the liver, supporting glycogen synthesis and storage [38]. Dietary oligosaccharides content in BC is around 1 g/L, about double the level compared to mature milk [39]. Most of them are not digested in the upper intestine, so they can play a prebiotic role, passing intact into the colon portion of the intestine, where they can represent a metabolic substrate for colonic bacteria [40]. Fat content in BC is around 7%; the lipid fraction contains several molecules of potential health relevance, including ω-3 and ω-6 essential fatty acids, conjugated linoleic acid, and phospholipids. The BC lipid profile is characterized by around 65–75% of saturated fatty acids, 24–28% monounsaturated fatty acids, and 4–5 polyunsaturated fatty acids [41]. Palmitic acid (about 40%) and oleic acid (21%) are the two most represented total fatty acids [40], confirming the importance of palmitic acid in infant nutrition [42], while oleic acid is involved in other health benefits related to the immunomodulation and to the cardiovascular system [43]. Fat-soluble (A, D, and E) and water-soluble (B-complex) vitamins are both represented in BC (Table 2), being involved in several metabolic processes including bone growth and antioxidant activity. Vitamin D plays also an important role in supporting immune system function and mental health [44]. Vitamins and minerals concentrations in BC are higher compared to mature milk [45,46] (Table 2).

The main role of Immunoglobulins in mammals is to transfer passive immunity from mother to newborn; the major immunoglobulin in BC is IgG, with a concentration of 30–87 g/L, about 80–90% of the total IgGs, while IgA, IgD, IgE, and IgM have been detected in smaller contents [45]. In humans, immunoglobulins can pass the placental barrier, while this is not possible in cows; for this reason, the only way to provide immunoglobulins for calves is by feeding them with BC, so IgG can provide passive immunity and modulate the innate immune systems [47]. Other molecules, besides immunoglobulins, involved in preventing and resolving microbial infections, have been detected in BC [48].

Lactoperoxidase shows an antimicrobial effect against several Gram-positive and Gram-negative bacteria [49], producing oxidative molecules able to interfere with specific amino acids in microbial proteins, causing a block of microbial metabolism and inhibiting consequently bacteria replication. Lysozymes show antibacterial activity, too, provoking two different effects: cell lysis of Gram-negative bacteria, and inhibition of Gram-positive bacteria growth [50]. Another bioactive peptide detected in colostrum is represented by Lactoferrin, an iron-binding glycoprotein (80 kDa) contained in both HC and BC; although, lactoferrin content in BC is only about 10% compared to HC [50]. Lactoferrin causes several effects, enhancing iron absorption as well as showing antimicrobial and immune-modulating activities, and stimulating the growth of intestinal epithelial cells and fibroblasts [51]. Lactoferrin in BC plays an important role in the regulation of gut growth in neonates, reducing mortality and increasing growth rate in calves, reducing infections of the respiratory tract [52].

3.2.1. Use of BC in Human Nutrition

BC has been used in human nutrition, for both children and adults, in the treatment of gastrointestinal and immune system diseases, allergies, and various infections, administering BC dietary supplements most of the time through drinks [53]. The antibacterial activity of BC can affect pathogen bacteria in the human intestine indirectly, by stimulating the growth of positive intestinal microorganisms, especially Bifidobacteria and Lactobacillus [54]. The human immune system receives signals from BC-based food, associated with the non-invasiveness of these food antigens, preventing in this way an abnormal immune reaction but supporting, on the other hand, the immune response against pathogens [55].

The positive effect of BC on the human body is shown during antibiotic therapy [56]. BC administration at the beginning of therapy will reduce the risk of diarrhea, with a beneficial effect on the intestinal microbiota, thereby enhancing immunity. Lactoferrin in BC leads to an increase in bacterial susceptibility to the antibiotic, increasing its antimicrobial activity [57]. It seems that colostrum should be avoided only for infants who have an allergy to milk or milk-based products. In general, BC is considered safe and well tolerated, showing several important nutritional constituents. For this reason, it is very important to perform further well-designed, double-blind, placebo-controlled studies using BC and/or specific colostrum-based foods to evaluate possible therapeutic uses in human nutrition.

Some authors have found beneficial effects of BC supplemented in male and female older adults during resistant training (60 g/d of colostrum). BC provoked an increase in leg press strength and reduced bone resorption, showing better results compared to patients receiving whey protein complex supplementation [58]. On the other hand, the improvement in cognitive function, lean tissue mass, muscle thickness, and upper body strength was evidenced both in subjects treated with colostrum and in those treated with the whey protein complex [58]. Other authors found that BC could be used to counteract the potential side effects of non-steroidal anti-inflammatory drugs (NSAIDs). In fact, BC has a good composition of growth factors (α-IGF-1, β-IGF-1, TGF, and EGF) able in stimulating the repair processes of the gastrointestinal (GI) tract and therefore could protect from NSAID-induced enteropathy [59].

Furthermore, BC has been used in clinical studies to evaluate its potential beneficial effect on the improvement of GI health and integrity, particularly in patients showing chronic or acute infections [60]. A recent study showed that a BC polyclonal antibody preparation could be useful to inhibit SARS-CoV-2 spread, in addition to vaccination and mask-wearing. These authors prepared a nasal spray formulation with the colostrum antibody preparation and described its bioavailability in the human nasal cavity demonstrating that this preparation, thanks to the presence of viscosity-increasing excipients that prolong the action time on the nasal mucosa, ensures successful delivery of the immunoglobulin preparation [61].

3.3. Donkey Colostrum

Donkey foals, because of the type of placentation, require a good amount of high-quality colostrum, to achieve an adequate serum IgG concentration at 24 h of life [62]. The donkey placenta, in fact, is diffuse, epitheliochorial, and shows several microplacentomes consisting of a fetal microcotyledonary and a maternal microcaruncular part [62]. A reduced consumption or the availability of low-quality colostrum in newborn foals can easily lead to common negative health conditions, provoking sepsis, which can manifest in several different ways, such as bacteremia, pneumonia, enterocolitis, and septic arthritis [62].

The chemical composition of the donkey milk changes quickly in the first week of lactation; in particular, donkey colostrum (DC) shows higher concentrations of protein, Igs, lactoferrin, β-lactoglobulin, and fat, and lower lactose content compared with mature milk, while lysozyme content is similar in both colostrum and mature milk [63]. Some authors have suggested that DC could be an appropriate substitute for HC, considering the high similarity in chemical composition between human milk and donkey milk. For these reasons, in several studies, children affected by Cow Milk Protein Allergy have been treated by administering donkey milk; this is considered by several pediatricians a natural and safe replacer of human milk in infant nutrition [64].

A detailed study was performed in order to determine the physico-chemical characteristics and somatic cell count of DC during the first ten days after foaling; a decreasing trend was observed for protein, dry matter, and ash levels [65]. The lowest values for lactose and pH were detected in the first hours (4.01 g/100 mL of milk and 6.69 pH units), while protein content showed a peak (10.2 g/100 mL of milk) at 0 h (Table 3). Basically, the colostrum phase in donkeys lasts about 12–24 h, after which the secretion can be considered transitional milk [25].

Several studies have been performed on donkey milk in order to evaluate its lipid content, characterized by a high percentage of essential fatty acids, with an n–3:n–6 series ratio of 0.86 [65]. DC mineral content emphasizes a balanced proportion of both macro-elements K, P, Ca, Mg, Na, and micro-elements, Cu, Zn, Ni, Cd, and Fe [66]. The most important nutritional characteristics of donkey milk can be attributed also to the health status of the donkey’s mammary gland, which is correlated to the innate immunity of donkey’s udders [67,68]. Lactoferrin, lactoperoxidase, and lysozyme are considered the most important bioactive peptides detected in donkey milk and donkey milk colostrum, considering their crucial role played as antimicrobial agents [48]. During the lactation period, these proteins show significant changes in their content; colostrum has higher lactoferrin and β-lactoglobulin concentrations compared to raw milk, while the lysozyme content has been determined at similar levels in colostrum and fresh mature milk [69].

Comparing the results determined in DC with the values identified in other mammals and humans (Table 1), it can be seen that DC shows great similarity with human and cow colostrum. Fat content in DC is very close to the fat content in cow colostrum and human colostrum [70], compared to the fat content of goat colostrum [71]. Protein content in DC is similar to the values reported for HC, while it is lower compared to the protein content of cow and she-goat colostrum (Table 1) [72].

3.4. Goat Colostrum

Colostrum chemical composition in various mammalian species differs significantly in nutrient content (Table 4); the variations determined in some ruminant species reflect different adaptive strategies [73]. Data are available for milks of nearly 200 of the more than 4000 existing mammalian species [74]. Milk water content ranges from about 90% (in kangaroo) to 34.6% (in fur seal), while fat content ranges from almost 1% (in donkey) to more than 50% (in fur seal); aquatic mammals typically have high milk fat content percentage. Milk protein content differs significantly among species but not so much as milk fat, ranging from approximately 1% (in human) to about 14% (in whale). Lactose ranges from trace (in kangaroo) to 7.4% (in donkey), while minerals range from almost 0 to 2% [75].

Goat colostrum (GC) is a good source of nutrients such as proteins, lactose, fat, and micronutrients including vitamins and minerals, and it is also characterized by several biologically active compounds [76]. These include antimicrobial proteins (Lactoferrin), Epidermal Growth Factor (EGF), Insulin-like Growth Factor-I (IGF-I), and Immunoglobulin G (IgG). GC shows (Table 5), compared to mature milk, significantly higher contents of protein, fat, minerals, Dry Matter, EGF, and IGF-I, while lactose concentration is lower. GC plays an important role in the nutrition, protection, and development of the newborn, taking part in the immunological defense of the kids, stimulating the immune system, or providing passive protection, especially in the gastrointestinal tract [77]. A large part of GC molecules come directly from the bloodstream (i.e., Ig, somatotropin, prolactin, insulin, and glucagon), while others (fat, lactose fat, lactose, caseins, α-lactalbumin, β-lactoglobulin, etc.) are produced directly in the udder from mammary epithelial cells and the stroma [78].

GC has been investigated in order to be used as a functional food, due to its antitumor activity and the ability to lower blood pressure [79]; the chemical composition of GC compared with goat mature milk is shown in Table 5. Compared with goat mature milk, GC shows significantly higher contents of protein (+144.57%), fat (+64.43%), minerals (+30.56%), and dry matter (+52.27%), but lower concentrations of lactose (−41.46%) [80].

GC contains high concentrations of Ca, P, and Mg, and low concentrations of Zn, Fe, Cd, As, Pb, and Hg [76]. Moreover, 25% of the fatty acids in GC belong to the category of unsaturated fatty acids, compared to 40.8% for bovine milk fat and 60.8% for human milk fat. In GC, BC, and HC, the ratios of saturated to unsaturated fatty acids were calculated, obtaining the values of 3.03 in GC, 1.10 in BC, and 0.57 in HC [80].

3.5. Alpaca Colostrum

Alpacas and llamas are domesticated species of South American Camelids [81]. Because of the epitheliochorial placenta of alpacas, their newborns lack gammaglobulins; therefore, they receive from their mothers’ high-quality colostrum to achieve passive humoral protection against infectious diseases via intestinal absorption [82]. When the alpaca mother does not provide enough colostrum, or poor quality colostrum, or, in the worst scenario, dies during parturition, it is important to provide good colostrum replacers for the newborns. To prepare colostrum replacers, it is important to know in detail the composition of alpacas’ colostrum.

The alpaca colostrum chemical composition is shown in Table 6. Fat content in colostrum increased significantly from day 1 to day 4, then the fat level was similar to the value determined in mature milk. Lactose content on the day of parturition was lower compared to the following days 2, 3, and 4. Colostrum protein content decreased significantly during the first 4 days but remained higher compared to the levels determined in mature milk [83]. The average total amount of colostrum hand collected from each animal was 20.8 mL, without significant differences among the days.

The fat, protein, and lactose content in alpacas’ colostrum changed substantially during the following lactation stages. The decrease in protein concentration and the increase in fat content confirm the trends registered in other mammalian species [84]. The significant decrease in protein content during the colostrum phase can be determined by the strong reduction in immunoglobulin concentration, which is a frequent condition in most of the colostrum produced by the most common dairy mammalian species [85].

3.6. Mare’s Colostrum

Mare’s colostrum is crucial during the first weeks of life for the foal; if the mare dies, it is essential that the foal receives a milk replacer adequate for its feeding requirements. The mares’ udder consists of two smaller caudal glands and two larger cranial glands, but sometimes six glands can occur [86]; each quarter consists of one gland cistern and one teat cistern. Mares’ milk can also represent an important food for the human population [87], especially in the feeding of children showing IgE-mediated cow milk allergy [88]. The average daily milk production for a lactating mare can be estimated at around 2–3.5% of the horse’s bodyweight per day, so a mare weighing 500 kg produces around 10–18 kg of milk per day [89].

The dry matter content in a mare’s colostrum is around 25% while the mare’s mature milk shows a dry matter content of 10–12%, which decreases throughout the lactation [90]. The fat content in the milk of mares is relatively low with an average of around 1–1.5% [91]. The fat content also varies during the lactation period, with an overall decrease in fat content from colostrum to the end of lactation [92]. Fat content in a mare’s colostrum is affected by the number of parturitions registered by the mare: the more the foals, the higher the fat content in the colostrum [93,94].

The protein in mares’ milk is on average close to 2%; this value decreases over the lactation period, and the highest decrease in protein occurs during the colostrum period [95]. Pre-albumin is a peptide belonging to the whey protein category and is only detected in the colostrum. Immunoglobulins also belong to whey proteins and show a high concentration at the beginning of the colostrum period, starting to decrease both during the colostrum phase and during the whole lactation period [96]. The content of the whey proteins α-globulins and albumins increase from the colostrum to the mature milk [97].

The carbohydrates in mares’ milk consist mostly of lactose with only a very small amount of glucose and galactose, with an average amount of lactose in milk close to 6%. In the first days of the lactation period, there is a low amount of lactose in colostrum, about 3.4%, which increases during the following weeks [98]. Vitamin and mineral content in mare’s colostrum is shown in Table 7. A diet rich in forage significantly affects calcium and phosphorus contents in both colostrum and mature mare’s milk compared to a diet rich in concentrate, while sodium, potassium, and magnesium concentrations are not affected by diet [99]. Different minerals show their peak at different times; the calcium peak is about a week after parturition, then it decreases, while phosphorus shows its peak within a couple of days, and then its level decreases, similar to other minerals such as magnesium, potassium, and sodium [100].

Vitamin content in mare’s colostrum and in mature milk is shown in Table 8; vitamin A and vitamin E contents were significantly lower in mature milk compared to the values determined in colostrum [102].

3.7. Ewe’s Colostrum

The importance of milk and dairy products in human nutrition has been well-known for a long time; for this reason, functional dairy foods are considered a novel attractive dietary option, having the advantage of being ‘‘natural’’ products, and therefore better accepted by consumers [104]. Most of the studies concerning dairy foods have focused on bovine milk, which is the most common milk used in human nutrition in a large part of the world [105]. In recent years, studies concerning the functional and nutritional attributes of milk from other mammalian species increased [106]. The use in human nutrition of milk from small ruminants, especially goat and ewe milk, has recently received special attention due to some interesting nutritional quality parameters affecting human health [107]. In fact, studies on the minor bioactive components of ewe and goat’s milk are still quite limited, such as the nutritional properties of small ruminant colostrum. In a study performed on ovine milk, colostrum collected from 84 Rambouillet primiparous ewes showed a yield on day 1 ranging from 378.4 to 579.3 g/d, with a protein content close to 16.6%, fat content around 12.5–14.1%, and lactose content of 2.32–2.62% [108]. Ewe’s mature milk was collected 20 days after parturition, and showed significant differences compared to colostrum: milk yield ranged from 749.2 to 960.8 g/d, protein content was 5.11–5.38%, fat concentration ranged from 5.66 to 6.60%, and lactose content was 5.10–5.20% [108]. Ewe’s colostrum shows the highest Total Solid content compared to other dairy ruminants such as cow or goat; lipid content was 9.11% for ewe’s colostrum and decreased to 5.65% for cow colostrum, and to 4.88% for goat colostrum [109]. Colostrum of Awassi ewes showed a content of 60.9 ± 21.4 mg/mL of IgG; colostrum obtained from primiparous ewes showed higher IgG levels compared to the values determined in multiparous ewes [109].

Interesting work has been performed to determine the polyamine concentrations in both ewe and goat colostrum and milk, on the first post-partum day and later after two weeks of lactation. Polyamine pool determination in both kinds of milk gave valuable scientific data concerning the dietary aspects of these two milk categories, creating the possibility of using them in the preparation of quality-oriented dairy products and introducing them in the market of novel dairy foods [107].

Putrescine was not detected in mature goat milk (15th day), while Spermidine was the most abundant polyamine in goat milk. In ewe’s milk, spermidine and spermine contents were comparable among colostrum and mature milk (Table 9). Mature ovine milk (15th day) showed higher polyamine content compared to goat milk, but caprine colostrum had a higher total polyamine content compared to ewe’s one.

The possibility of creating novel dairy foods with enhanced nutritional benefits for specific consumer categories is really appealing. Furthermore, the possibility of using ewe or goat milk or their colostrum in clinical trials is very interesting, due to the important role these nonpeptide nitrogenous molecules play in homeostatic cell regulation.

3.8. Camel’s Colostrum

The use of non-bovine milk for feeding children can be effective in reducing the development of gastrointestinal disorders [110]. Goat milk was investigated firstly, and later in the 1990s, donkey milk started to arouse great interest in clinical trials [110]. Recently, the use of camel milk to replace dairy cows and other kinds of milk (goat, donkey, and mare) has attracted interest in the scientific community [111]. Camel milk’s antiallergenic properties are also due to the similar protein profile compared to human mother’s milk, with the absence of β-lactoglobulin and a high concentration of α-lactalbumin [112]. Camel whey protein shows a high content of anti-microbial factors such as lysozyme, lactoferrin, and immunoglobulins [113,114]; other whey proteins have been identified in camel milk including serum albumin, immunoglobulins, lactophorin, and peptidoglycan recognition protein [115]. Considering the different chemical composition of camel colostrum and camel mature milk, fat and protein contents decrease greatly in the post-partum period: seven days after calving, total fat fell to an eighth of its previous value (25.9% vs. 3.1%), while total protein was divided by four, falling from 17.2% to 4.2% (Table 10). Lactose concentration showed values very close to each other, without significant differences among different animals (Table 10). In camel colostrum, any significant difference was observed regarding the Non-Protein-Nitrogen content, which remained stable all through the lactation period [116].

4. Conclusions

Colostrum contains all essential nutrients for the neonate during the first days of life, influencing the growth of mammalian newborns for several weeks and/or months beyond these first days. Bovine colostrum (BC) has been widely used for human consumption due to the high concentrations of bioactive peptides, vitamins, minerals, and growth factors, as well as free and conjugated oligosaccharides. BC is a functional food providing several benefits for human health, consumed by humans whether as dairy products or dietary supplements. As previously discussed in Section 3.2.1, BC has been exploited as a functional ingredient in foods such as cheeses, yogurts, ice cream, and ready-to-drink beverages. BC for human use and for clinical trials is either a complete BC powder or skimmed. Other foods include BC from which caseins and lactalbumin have been removed, or foods in which immunoglobulins and growth factors have been added.

This review shows the macro-and micronutrient composition of colostrum produced by different mammalian species, describing bioactive molecules found in different colostrums and their potential for human nutrition. Important gaps in colostrum knowledge still remain, so further studies are necessary in order to take advantage of the different colostrums available on the market as a component of a healthy diet targeted at a variety of relevant human populations.

Author Contributions

Conceptualization, P.P. and S.V.; data curation, P.P. and S.V.; writing—original draft preparation, G.S.; writing—review and editing, Y.K.; visualization, J.-J.Z.; supervision, R.R. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

Not applicable.

Acknowledgments

A special thank is due to Natalina Cammertoni for her technical help in reference data collections.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Tables

Table 1

Chemical composition in colostrum from different mammalian species.

Colostrum	Fat	Protein	Lactose
Human (g/100 g) [3]	3.8	1.2	7.0
Human (g/100 mL) [24]	3–5	0.8–0.9	6.9–7.2
Cow (g/100 g) [3]	3.8	3.3	4.8
Cow (g/100 mL) [24]	6.7	14.9	2.5
Goat (g/100 g) [24]	4.1	3.4	4.7
Donkey 24 h (g/100 mL) [25]	2.08	2.79	5.30
Donkey 6 d (g/100 mL) [25]	1.33	2.53	5.60

Table 2

Minerals and Vitamins content in BC and in mature milk [32].

Minerals	BC	Mature Milk
Calcium (g/kg)	2.6–4.7	1.2–1.3
Phosphorus (g/kg)	4.5	0.9–1.2
Potassium (g/kg)	1.4–2.8	1.5–1.7
Sodium (g/kg)	0.7–1.1	0.4
Magnesium (g/kg)	0.4–0.7	0.1
Zinc (mg/kg)	11.6–38.1	3–6
Vitamins
Thiamine—Vitamin B1 (µg/mL)	0.58–0.90	0.4–0.5
Riboflavin—Vitamin B2 (µg/mL)	4.55–4.83	1.5–1.7
Niacin—Vitamin B3 (µg/mL)	0.34–0.96	0.8–0.9
Cobalamin—Vitamin B12 (µg/mL)	0.05–0.60	0.004–0.006
Vitamin A (µg/100 mL)	25	34
Vitamin D (IU/g fat)	0.89–1.81	0.41
Tocopherol—Vitamin E (µg/g)	2.92–5.63	0.06

Table 3

DC chemical and physical composition during the first ten day of lactation.

Lactation Stage	0 h	24 h	48 h	4 d	6 d	8 d	10 d
pH	6.69	6.73	6.70	6.76	6.94	7.03	6.96
DM (g/100 mL)	18.9	12.4	12.5	12.4	12.6	11.2	11.2
Lactose (g/100 mL)	4.01	5.30	5.01	5.83	5.60	6.04	5.90
Fat (g/100 mL)	2.04	2.08	1.84	1.58	1.33	1.05	1.31
Protein (g/100 mL)	10.2	2.79	2.89	2.75	2.53	2.33	2.21
Somatic Cells Count (cells/mL × 1000)	221	451	231	220	223	254	215

DM: Dry Matter. Source: [25].

Table 4

Colostrum chemical composition in exotic ruminant species.

Species	Fat	Protein	Lactose
Buffalo (g/100 g) [70]	5.44	18.75	2.70
Buffalo (g/100 g) [19]	7.56–11.3	4.3	4.7
Yak (g/100 g) [70]	14.0	16.1	1.90
Dromedary (g/100 g) [72]	1.50	13.0	3.60
Camel (g/100 g) [76]	0.30	19.2	5.90
Llama (g/100 g) [79]	0.75	16.8	4.12
Elephant (g/kg) [70]	56.0	21.0	61.8

Table 5

Chemical composition of GC and goat mature milk.

Milk Nutrient	Goat Colostrum	Goat Mature Milk
Protein (g/100 g)	8.78	3.59
Fat (g/100 g)	6.61	4.02
Lactose (g/100 g)	2.64	4.51
Minerals (g/100 g)	0.94	0.72
Dry Matter (g/100 g)	19.14	12.57
IgG (µg/mL)	8123.33	1706.33

Source: [80].

Table 6

Chemical composition of alpaca colostrum during the first 4 days post-partum.

Colostrum	Day 1	Day 2	Day 3	Day 4
Protein (%)	20.4	10.4	9.48	8.30
Fat (%)	0.51	2.01	2.78	5.31
Lactose (%)	3.95	5.23	4.84	5.01

Source: [83].

Table 7

Minerals content in mare’s colostrum and mature milk (µg/g).

Mineral	Colostrum	Mature Milk
Calcium (Ca)	748–847	614–700
Phosphorus (P)	389–742	216–540
Potassium (K)	928–1143	341–370
Magnesium (Mg)	140–473	43
Sodium (Na)	320–524	115–161
Zinc (Zn)	2.95–6.40	1.80–2.40
Iron (Fe)	1.00–1.31	0.49
Copper (Cu)	0.61–0.99	0.20–0.28

Source: [101].

Table 8

Vitamins content in mare’s colostrum and mature milk (mg/kg).

Vitamin	Colostrum	Mature Milk
Vitamin A	0.88	0.34
Vitamin D3	0.0054	0.0032
Vitamin E	1.342	1.128
Vitamin K3	0.043	0.029
Vitamin C	23.8	17.2

Source: [103].

Table 9

Polyamine (PA) concentration in ewe and goat colostrum and mature milk (µmol/L).

Species	Lactation Day	Putrescine	Spermidine	Spermine	Total PA
Ewe	1	0.11	0.37	0.50	0.95
	15	0.15	0.48	0.53	1.04
Goat	1	0.16	0.60	0.53	1.11
	15	0.00	0.31	0.25	0.79

Source: [107].

Table 10

Chemical composition of camel colostrum (g/100 g).

Nutrient	Mean	Minimum	Maximum
Total Protein	6.06	3.19	17.20
Fat	7.88	1.56	25.94
Lactose	3.63	---	---
Skimmed Dry Matter	15.61	9.79	41.1

Source: [115].

References

1. Fiocchi, A.; Dahda, L.; Dupont, C.; Campoy, C.; Fierro, V.; Nieto, A. Cow’s milk allergy: Towards an update of DRACMA guidelines. World Allergy Organ. J.; 2016; 9, 35. [DOI: https://dx.doi.org/10.1186/s40413-016-0125-0] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27895813]

2. Alves, A.C.; Alves, N.G.; Ascari, I.J.; Junqueira, F.B.; Coutinho, A.S.; Lima, R.R.; Perez, J.R.O.; De Paula, S.O.; Furusho-Garcia, I.F.; Abreu, L.R. Colostrum composition of Santa Ines sheep and passive transfer of immunity to lambs. J. Dairy Sci.; 2015; 68, pp. 3706-3716. [DOI: https://dx.doi.org/10.3168/jds.2014-7992] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25828655]

3. Ahmadi, M.; Boldura, O.; Milovanov, C.; Dronca, D.; Mircu, C.; Hutu, I.; Popescu, S.; Pădeanu, I.; Tulcan, C. Colostrum from Different Animal Species–A Product for Health Status Enhancement. Bullet. UASVM Anim. Sci. Biotechnol.; 2016; 73, pp. 95-100. [DOI: https://dx.doi.org/10.15835/buasvmcn-asb:11949]

4. Vatankhah, M. Relationship between Immunoglobulin concentration in the ewe’s serum and colostrum, and lamb’s serum in Lori-Bakhtiari Sheep. Iran. J. Appl. Anim. Sci.; 2013; 3, pp. 539-544.

5. Mehra, R.; Singh, R.; Nayan, V.; Buttar, H.S.; Kumar, N.; Kumar, S.; Bhardwaj, A.; Kaushik, R.; Kumar, H. Nutritional attributes of bovine colostrum components in human health and disease: A comprehensive review. Food Biosci.; 2021; 40, 100907. [DOI: https://dx.doi.org/10.1016/j.fbio.2021.100907]

6. Martin, C.R.; Ling, P.R.; Blackburn, G.L. Review of infant feeding: Key features of breast milk and infant formula. Nutrients; 2016; 8, 279. [DOI: https://dx.doi.org/10.3390/nu8050279]

7. Arenz, S.; Rückerl, R.; Koletzko, B.; Von Kries, R. Breast-feeding and childhood obesity—A systematic review. Int. J. Obes.; 2004; 28, pp. 1247-1256. [DOI: https://dx.doi.org/10.1038/sj.ijo.0802758]

8. Belfort, M.B. The Science of Breastfeeding and Brain Development. Breastfeed. Med.; 2017; 12, pp. 459-461. [DOI: https://dx.doi.org/10.1089/bfm.2017.0122]

9. Peila, C.; Moro, G.E.; Bertino, E.; Cavallarin, L.; Giribaldi, M.; Giuliani, F.; Cresi, F.; Coscia, A. The Effect of Holder Pasteurization on Nutrients and Biologically-Active Components in Donor Human Milk: A Review. Nutrients; 2016; 8, 477. [DOI: https://dx.doi.org/10.3390/nu8080477]

10. Peila, C.; Sottemano, S.; Cesare Marincola, F.; Stocchero, M.; Pusceddu, N.G.; Dessì, A.; Baraldi, E.; Fanos, V.; Bertino, E. NMR Metabonomic Profile of Preterm Human Milk in the First Month of Lactation: From Extreme to Moderate Prematurity. Foods; 2022; 11, 345. [DOI: https://dx.doi.org/10.3390/foods11030345]

11. Caba-Flores, M.D.; Ramos-Ligonio, A.; Camacho-Morales, A.; Martínez-Valenzuela, C.; Viveros-Contreras, R.; Caba, M. Breast Milk and the Importance of Chrononutrition. Front. Nutr.; 2022; 12, 867507. [DOI: https://dx.doi.org/10.3389/fnut.2022.867507] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35634367]

12. Bode, L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology; 2012; 22, pp. 1147-1162. [DOI: https://dx.doi.org/10.1093/glycob/cws074]

13. Fidler, N.; Koletzko, B. The fatty acid composition of human colostrum. Eur. J. Nutr.; 2000; 39, pp. 31-37. [DOI: https://dx.doi.org/10.1007/s003940050073] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10900555]

14. Gibson, R.A.; Kneebone, G.M. Fatty acid composition of human colostrum and mature breast milk. Am. J. Clin. Nutr.; 1981; 34, pp. 252-257. [DOI: https://dx.doi.org/10.1093/ajcn/34.2.252]

15. Rønneberg, R.; Skåra, B. Essential fatty acids in human colostrum. Acta Pediatr.; 1992; 81, pp. 779-783.

16. Serra, G.; Marletta, A.; Bonacci, W.; Campone, F.; Bertini, I.; Lantieri, P.; Risso, D.; Ciangherotti, S. Fatty acid composition of human milk in Italy. Biol. Neonate.; 1997; 72, pp. 1-8. [DOI: https://dx.doi.org/10.1159/000244459] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9313828]

17. Hurley, W.L.; Theil, P.K. Perspectives on immunoglobulins in colostrum and milk. Nutrients; 2011; 3, pp. 442-474. [DOI: https://dx.doi.org/10.3390/nu3040442] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22254105]

18. Civra, A.; Francese, R.; Donalisio, M.; Tonetto, P.; Coscia, A.; Sottemano, S.; Balestrini, R.; Faccio, A.; Cavallarin, L.; Moro, G.E. et al. Human Colostrum and Derived Extracellular Vesicles Prevent Infection by Human Rotavirus and Respiratory Syncytial Virus in Vitro. J. Human Lactat.; 2021; 37, pp. 122-134. [DOI: https://dx.doi.org/10.1177/0890334420988239]

19. Thapa, B.R. Health Factors in Colostrum. Indian J. Pediatr.; 2005; 72, pp. 579-581. [DOI: https://dx.doi.org/10.1007/BF02724182]

20. Cohen, S.M. Jaundice in the full-term newborn. Pediatr. Nurs.; 2006; 32, pp. 202-208.

21. Morris, J.A.; Wray, C.; Sojka, W.J. Passive protection of lambs against enteropathogenic Escherichia coli: Role of antibodies in serum and colostrums. J. Med. Microbiol.; 1980; 13, pp. 265-271. [DOI: https://dx.doi.org/10.1099/00222615-13-2-265] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/6991697]

22. Stephan, W.; Dichtelmuller, H.; Lissner, R. Antibodies from colostrum in oral immunotherapy. J. Clin. Chem. Clin. Biochem.; 1990; 28, 1923.

23. Van Hooijdonk, A.C.; Kussendrager, K.D.; Steijns, J.M. In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defence. Br. J. Nutr.; 2000; 84, pp. S127-S134. [DOI: https://dx.doi.org/10.1017/S000711450000235X] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11242457]

24. Bagwe, S.; Tharappel, L.J.P.; Kaur, G.; Buttar, H.S. Bovine colostrum: An emerging nutraceutical. J. Complement. Integr. Med.; 2015; 12, pp. 175-185. [DOI: https://dx.doi.org/10.1515/jcim-2014-0039]

25. Martini, M.; Licitra, R.; Altomonti, I.; Salari, F. Quality of donkey mammary secretion during the first ten days of lactation. Int. Dairy J.; 2020; 109, 104781. [DOI: https://dx.doi.org/10.1016/j.idairyj.2020.104781]

26. Wen, L.; Wu, Y.; Yang, Y.; Han, T.; Wang, W.; Fu, H.; Zheng, Y.; Shan, T.; Chen, J.; Xu, P. et al. Gestational Diabetes Mellitus Changes the Metabolomes of Human Colostrum, Transition Milk and Mature Milk. Med. Sci. Monit.; 2019; 25, pp. 6128-6152. [DOI: https://dx.doi.org/10.12659/MSM.915827]

27. Sangild, P.T.; Vonderohe, C.; Melendez Hebib, V.; Burrin, D.G. Potential Benefits of Bovine Colostrum in Pediatric Nutrition and Health. Nutrients; 2021; 13, 2551. [DOI: https://dx.doi.org/10.3390/nu13082551]

28. Ginger, M.R.; Grigor, M.R. Comparative aspects of milk caseins. Comp. Biochem. Physiol. B Biochem. Mol. Biol.; 1999; 124, pp. 133-145. [DOI: https://dx.doi.org/10.1016/S0305-0491(99)00110-8]

29. Contarini, G.; Povolo, M.; Pelizzola, V.; Monti, L.; Bruni, A.; Passolungo, L.; Abeni, F.; Degano, L. Bovine colostrum: Changes in lipid constituents in the first 5 days after parturition. J. Dairy Sci.; 2014; 97, pp. 5065-5072. [DOI: https://dx.doi.org/10.3168/jds.2013-7517]

30. Lönnerdal, B. Nutritional and phyisiologic significance of human milk proteins. Am. J. Clin. Nutr.; 2003; 77, pp. 1537S-1543S. [DOI: https://dx.doi.org/10.1093/ajcn/77.6.1537S]

31. Kanwar, J.; Kanwar, R.; Sun, X.; Punj, V.; Matta, H.; Morley, S.; Parratt, A.; Puri, M.; Sehgal, R. Molecular and Biotechnological Advances in Milk Proteins in Relation to Human Health. Curr. Protein Peptide Sci.; 2009; 10, pp. 308-338. [DOI: https://dx.doi.org/10.2174/138920309788922234] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19689355]

32. Playford, R.J.; Weiser, M.J. Bovine Colostrum: Its Constituents and Uses. Nutrients; 2021; 13, 265. [DOI: https://dx.doi.org/10.3390/nu13010265] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33477653]

33. Shah, N.P. Effects of milk-derived bioactives: An overview. Br. J. Nutr.; 2000; 84, pp. 3-10. [DOI: https://dx.doi.org/10.1017/S000711450000218X] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11242440]

34. Bastian, S.E.P.; Dunbar, A.J.; Priebe, I.K.; Owens, P.C.; Goddard, C. Measurement of betacellulin levels in bovine serum, colostrum and milk. J. Endocrinol.; 2001; 168, pp. 203-212. [DOI: https://dx.doi.org/10.1677/joe.0.1680203]

35. Matsumoto, H.; Shimokawa, Y.; Ushida, Y.; Toida, T.; Hayasawa, H. New Biological Function of Bovine α-Lactalbumin: Protective Effect against Ethanol- and Stress-induced Gastric Mucosal Injury in Rats. Biosci. Biotechnol. Biochem.; 2001; 65, pp. 1104-1111. [DOI: https://dx.doi.org/10.1271/bbb.65.1104]

36. Kehoe, S.I.; Jayarao, B.M.; Heinrichs, A.J. A survey of bovine colostrum composition and colostrum management practices on Pennsylvania dairy farms. J. Dairy Sci.; 2007; 90, pp. 4108-4116. [DOI: https://dx.doi.org/10.3168/jds.2007-0040]

37. Urashima, T.; Saito, T.; Nakamura, T.; Messer, M. Oligosaccharides of milk and colostrum in non-human mammals. Glycoconj. J.; 2001; 18, pp. 357-371. [DOI: https://dx.doi.org/10.1023/A:1014881913541]

38. Coelho, A.I.; Berry, G.T.; Rubio-Gozalbo, M.E. Galactose metabolism and health. Curr. Opin. Clin. Nutr. Metab. Care; 2015; 18, pp. 422-427. [DOI: https://dx.doi.org/10.1097/MCO.0000000000000189]

39. Ten Bruggencate, S.J.; Bovee-Oudenhoven, I.M.; Feitsma, A.L.; van Hoffen, E.; Schoterman, M.H. Functional role and mechanisms of sialyllactose and other sialylated milk oligosaccharides. Nutr. Rev.; 2014; 72, pp. 377-389. [DOI: https://dx.doi.org/10.1111/nure.12106]

40. Zivkovic, A.M.; Barile, D. Bovine milk as a source of functional oligosaccharides for improving human health. Adv. Nutr.; 2011; 2, pp. 284-289. [DOI: https://dx.doi.org/10.3945/an.111.000455]

41. O’Callaghan, T.F.; O’Donovan, M.; Murphy, J.P.; Sugrue, K.; Mannion, D.; McCarthy, W.P.; Timlin, M.; Kilcawley, K.N.; Hickey, R.M.; Tobin, J.T. Evolution of the bovine milk fatty acid profile—From colostrum to milk five days post parturition. Int. Dairy J.; 2020; 104, pp. 8721-8731. [DOI: https://dx.doi.org/10.1016/j.idairyj.2020.104655]

42. Miles, E.A.; Calder, P.C. The influence of the position of palmitate in infant formula triacylglycerols on health outcomes. Nutr. Res.; 2017; 44, pp. 1-8. [DOI: https://dx.doi.org/10.1016/j.nutres.2017.05.009] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28821313]

43. Sales-Campos, H.; Reis de Souza, P.; Crema Peghini, B.; Santana da Silva, J.; Ribeiro Cardoso, C. An Overview of the Modulatory Effects of Oleic Acid in Health and Disease. Mini Rev. Med. Chem.; 2013; 13, pp. 201-210.

44. Polzonetti, V.; Pucciarelli, S.; Vincenzetti, S.; Polidori, P. Dietary Intake of Vitamin D from Dairy Products Reduces the Risk of Osteoporosis. Nutrients; 2020; 12, 1743. [DOI: https://dx.doi.org/10.3390/nu12061743] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32532150]

45. Godden, S.M.; Lombard, J.E.; Woolums, A.R. Colostrum Management for Dairy Calves. Vet. Clin. N. Am. Food Anim. Pract.; 2019; 35, pp. 535-556. [DOI: https://dx.doi.org/10.1016/j.cvfa.2019.07.005]

46. Cleminson, J.S.; Zalewski, S.P.; Embleton, N.D. Nutrition in the preterm infant: What’s new?. Curr. Opin. Clin. Nutr. Metab. Care; 2016; 19, pp. 220-225. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27504517]

47. Ulfman, L.H.; Leusen, J.H.W.; Savelkoul, H.F.J.; Warner, J.O.; van Neerven, R.J.J. Effects of Bovine Immunoglobulins on Immune Function, Allergy, and Infection. Front. Nutr.; 2018; 5, pp. 1-20. [DOI: https://dx.doi.org/10.3389/fnut.2018.00052]

48. Vincenzetti, S.; Pucciarelli, S.; Polzonetti, V.; Polidori, P. Role of Proteins and of Some Bioactive Peptides on the Nutritional Quality of Donkey Milk and Their Impact on Human Health. Beverages; 2017; 3, 34. [DOI: https://dx.doi.org/10.3390/beverages3030034]

49. Seifu, E.; Buys, E.M.; Donkin, E.F. Significance of the lactoperoxidase system in the dairy industry and its potential applications: A review. Trends Food Sci. Technol.; 2005; 16, pp. 137-145. [DOI: https://dx.doi.org/10.1016/j.tifs.2004.11.002]

50. Wheeler, T.T.; Hodgkinson, A.J.; Prosser, C.G.; Davis, S.R. Immune components of colostrum and milk—A historical perspective. J. Mammary Gland Biol. Neoplasia; 2007; 12, pp. 237-247. [DOI: https://dx.doi.org/10.1007/s10911-007-9051-7]

51. Clare, D.; Catignani, G.; Swaisgood, H. Biodefense Properties of Milk: The Role of Antimicrobial Proteins and Peptides. Curr. Pharm. Des.; 2005; 9, pp. 1239-1255. [DOI: https://dx.doi.org/10.2174/1381612033454874] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12769734]

52. Zhao, X.; Xu, X.-X.; Liu, Y.; Xi, E.-Z.; An, J.-J.; Tabys, D.; Liu, N. The In Vitro Protective Role of Bovine Lactoferrin on Intestinal Epithelial Barrier. Molecules; 2019; 24, 148. [DOI: https://dx.doi.org/10.3390/molecules24010148] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30609730]

53. King, J.C.; Cummings, G.E.; Guo, N.; Trivedi, L.; Readmond, B.X.; Keane, V.; Feigelman, S.; de Waard, R. A double-blind, placebo-controlled, pilot study of bovine lactoferrin supplementation in bottle-fed infants. J. Pediatr. Gastroenterol. Nutr.; 2007; 44, pp. 245-251. [DOI: https://dx.doi.org/10.1097/01.mpg.0000243435.54958.68]

54. Conte, F.; Scarantino, S. A study on the quality of bovine colostrum: Physical, chemical and safety assessment. Int. Food Res. J.; 2013; 20, pp. 925-931.

55. Benson, K.F.; Carter, S.G.; Patterson, K.M.; Patel, D.; Jensen, G.S. A novel extract from bovine colostrum whey supports antibacterial and anti-viral innate immune functions in vitro and in vivo I. Enhanced immune activity in vitro translates to improved microbial clearance in animal infection models. Prev. Med.; 2011; 54, pp. 116-123. [DOI: https://dx.doi.org/10.1016/j.ypmed.2011.12.023]

56. Dzik, S.; Miciński, B.; Aitzhanova, I.; Miciński, J.; Pogorzelska, J.; Beisenov, A.; Kowalski, I.M. Properties of bovine colostrum and the possibilities of use. Pol. Ann. Medic.; 2017; 24, pp. 295-299. [DOI: https://dx.doi.org/10.1016/j.poamed.2017.03.004]

57. Wong, E.B.; Mallet, J.F.; Duarte, J.; Matar, C.; Ritz, B.W. Bovine colostrum enhances natural killer cell activity and immune response in a mouse model of influenza infection and mediates intestinal immunity through toll-like receptors 2 and 4. J. Food Nutr. Res.; 2014; 34, pp. 318-325. [DOI: https://dx.doi.org/10.1016/j.nutres.2014.02.007]

58. Diarra, M.; Petitclerc, D.; Lacasse, P. Effect of lactoferrin in combination with penicillin on the morphology and the physiology of Staphylococcus aureus isolated from bovine mastitis. J. Dairy Sci.; 2002; 85, pp. 1141-1149. [DOI: https://dx.doi.org/10.3168/jds.S0022-0302(02)74176-3]

59. Arslan, A.; Kaplan, M.; Duman, H.; Bayraktar, A.; Ertürk, M.; Henrick, B.M.; Frese, S.A.; Karav, S. Bovine Colostrum and Its Potential for Human Health and Nutrition. Front. Nutr.; 2021; 21, 651721. [DOI: https://dx.doi.org/10.3389/fnut.2021.651721]

60. Mehra, R.; Marnila, P.; Korhonen, H. Milk immunoglobulins for health promotion. Int. Dairy J.; 2006; 16, pp. 1262-1271. [DOI: https://dx.doi.org/10.1016/j.idairyj.2006.06.003]

61. Kangro, K.; Kurašin, M.; Gildemann, K.; Sankovski, E.; Žusinaite, E.; Lello, L.S.; Pert, R.; Kavak, A.; Poikalainen, V.; Lepasalu, L. et al. Bovine colostrum-derived antibodies against SARS-CoV-2 show great potential to serve as prophylactic agents. PLoS ONE; 2022; 10, e0268806. [DOI: https://dx.doi.org/10.1371/journal.pone.0268806] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35687549]

62. Marchis, Z.; Odagiu, A.; Coroian, A.; Oroian, I.; Mirza, M.; Burduhos, P. Analysis of environmental factors’ impact on donkeys’ colostrum quality. Sustainability; 2018; 10, 2958. [DOI: https://dx.doi.org/10.3390/su10092958]

63. Martini, M.; Altomonte, I.; Licitra, R.; Salari, F. Nutritional and nutraceutical quality of donkey milk. J. Equine Vet. Sci.; 2018; 65, pp. 33-37. [DOI: https://dx.doi.org/10.1016/j.jevs.2017.10.020]

64. Turini, L.; Bonelli, F.; Nocera, I.; Meucci, V.; Conte, G.; Sgorbini, M. Evaluation of Different Methods to Estimate the Transfer of Immunity in Donkey Foals Fed with Colostrum of Good IgG Quality: A Preliminary Study. Animals; 2021; 11, 507. [DOI: https://dx.doi.org/10.3390/ani11020507]

65. Salimei, E.; Fantuz, F.; Coppola, R.; Chiofalo, B.; Polidori, P.; Varisco, G. Composition and characteristics of ass’s milk. Anim. Res.; 2004; 53, pp. 67-78. [DOI: https://dx.doi.org/10.1051/animres:2003049]

66. Zhang, X.Y.; Zhao, L.; Jiang, L.; Dong, M.L.; Ren, F.Z. The antimicrobial activity of donkey milk and microflora changes during storage. Food Control; 2008; 19, pp. 1191-1195. [DOI: https://dx.doi.org/10.1016/j.foodcont.2008.01.005]

67. Pilla, R.; Daprà, V.; Zecconi, A.; Piccinini, R. Hygienic and health characteristics of donkey milk during a follow-up study. J. Dairy Res.; 2010; 77, pp. 392-397. [DOI: https://dx.doi.org/10.1017/S0022029910000221]

68. Vincenzetti, S.; Polidori, P.; Mariani, P.; Cammertoni, N.; Fantuz, F.; Vita, A. Donkey’s milk protein fractions characterization. Food Chem.; 2008; 106, pp. 640-649.

69. Meyer, H.; Kamphues, J. Grundlagen der Ernahrung von Neugeborenen. Neugeborenen-und Sauglingskunde der Tiere; 2nd ed. Walser, K.; Bostedt, H. Ferdinand Enke Verlag: Stuttgart, Germany, 1990; pp. 55-71.

70. Park, Y.W. Minor species milk. Handbook of Milk of Non-Bovine Mammals; 1st ed. Park, Y.W.; Haenlein, G.F.W. Blackwell Publishing: Ames, IA, USA, 2006; pp. 393-406.

71. Tsioulpas, A.; Grandison, A.S.; Lewis, M.J. Changes in physical properties of bovine milk from the colostrum period to early lactation. J. Dairy Sci.; 2007; 90, pp. 5012-5017. [DOI: https://dx.doi.org/10.3168/jds.2007-0192]

72. Bernabucci, U.; Basiricò, R.; Morera, P. Impact of Hot Environment on Colostrum and Milk Composition. Cell. Mol. Biol.; 2013; 59, pp. 67-83.

73. Merin, U.; Bernstein, S.; Van Creveld, C.; Yagil, R.; Gollop, N. Camel (Camelus dromedarius) colostrum and milk composition during the lactation. Milchwiss; 2001; 50, pp. 70-73.

74. Jandal, J.M. Comparative aspects of goat and sheep milk. Small Rum. Res.; 1996; 22, pp. 177-185. [DOI: https://dx.doi.org/10.1016/S0921-4488(96)00880-2]

75. Barowicz, T.; Migdał, W.; Pietras, M.; Živković, B. Chemical composition of colostrum and milk of sows feed conjugated linoleic acid (CLA) during last period of pregnancy. Biotech. Anim. Husb.; 2002; 18, pp. 27-32. [DOI: https://dx.doi.org/10.2298/BAH0204027B]

76. Kracmar, S.; Kuchtık, J.; Baran, M.; Varadyov, Z.; Kracmarova, E.; Gajdusek, S.; Jelınek, P. Dynamics of changes in contents of organic and inorganic substances in sheep colostrum within the first 72 h after parturition. Small Rum. Res.; 2005; 56, pp. 183-188. [DOI: https://dx.doi.org/10.1016/j.smallrumres.2004.06.012]

77. Playford, R.J. Peptide therapy and the gastroenterologist: Colostrums and milk-derived growth factors. Clin. Nutr.; 2001; 20, pp. 101-106. [DOI: https://dx.doi.org/10.1054/clnu.2001.0434]

78. Liu, Y.; Cai, J.; Zhang, F. Influence of goat colostrum and mature milk on intestinal microbiota. J. Funct. Foods; 2021; 86, 104704. [DOI: https://dx.doi.org/10.1016/j.jff.2021.104704]

79. Soloshenko, K.I.; Lych, I.V.; Voloshyna, I.M.; Shkotova, L.V. Polyfunctional properties of goat colostrum proteins and their use. Biopol. Cell.; 2020; 36, pp. 197-209. [DOI: https://dx.doi.org/10.7124/bc.000A2B]

80. Niznikowski, R.; Popielarczyk, D.; Strzelec, E.; Wojtowski, J.; Dankow, R.; Pikul, J.; Goslawski, W.; Kuczynska, B. The effect of early colostrums collection on selected performance traits in sheep. Arch. Tierz.; 2006; 49, pp. 226-230.

81. Polidori, P.; Antonini, M.; Torres, D.; Beghelli, D.; Renieri, C. Tenderness evaluation and mineral levels of llama (Lama glama) and alpaca (Lama pacos) meat. Meat Sci.; 2007; 77, pp. 599-601. [DOI: https://dx.doi.org/10.1016/j.meatsci.2007.05.011]

82. Mößler, M.; Rychli, K.; Reichmann, V.M.; Albert, T.; Wittek, T. Immunoglobulin G Concentrations in Alpaca Colostrum during the First Four Days after Parturition. Animals; 2022; 12, 167. [DOI: https://dx.doi.org/10.3390/ani12020167]

83. Mößler, M.; Aichner, J.; Müller, A.; Albert, T.; Wittek, T. Concentrations of Fat, Protein, Lactose, Macro and Trace Minerals in Alpaca Colostrum and Milk at Different Lactation Stages. Animals; 2021; 11, 1955. [DOI: https://dx.doi.org/10.3390/ani11071955] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34208867]

84. Sánchez-Macías, D.; Moreno-Indias, I.; Castro, N.; Morales-Delanuez, A.; Argüello, A. From goat colostrum to milk: Physical, chemical, and immune evolution from partum to 90 days postpartum. J. Dairy Sci.; 2014; 97, pp. 10-16. [DOI: https://dx.doi.org/10.3168/jds.2013-6811] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24183682]

85. Mi, J.D.; Zhou, J.W.; Ding, L.M.; Wang, L.; Long, R.J. Short communication: Changes in the composition of yak colostrum during the first week of lactation. J. Dairy Sci.; 2016; 99, pp. 818-824. [DOI: https://dx.doi.org/10.3168/jds.2015-9824] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26547651]

86. Csapó-Kiss, Z.; Stefler, J.; Martin, T.G.; Makray, S.; Csapó, J. Composition of Mares’ Colostrum and Milk. Protein Content, Amino Acid Composition and Contents of Macro and Micro-elements. Int. Dairy J.; 1995; 5, pp. 403-415. [DOI: https://dx.doi.org/10.1016/0958-6946(94)00014-G]

87. Polidori, P.; Cammertoni, N.; Santini, G.; Klimanova, Y.; Zhang, J.-J.; Vincenzetti, S. Nutritional Properties of Camelids and Equids Fresh and Fermented Milk. Dairy; 2021; 2, pp. 288-302. [DOI: https://dx.doi.org/10.3390/dairy2020024]

88. Businco, L.; Giampietro, P.G.; Lucenti, P.; Lucaroni, F.; Pini, C.; Di Felice, G.; Iacovacci, P.; Curadi, C.; Orlandi, M. Allergenicity of mare’s milk in children with cow’s milk allergy. J. Allergy Clin. Immunol.; 2000; 105, pp. 1031-1034. [DOI: https://dx.doi.org/10.1067/mai.2000.106377]

89. Csapó, J.; Stefler, J.; Martin, T.G.; Makray, S.; Csapó-Kiss, Z. Composition of Mares’ Colostrum and Milk. Fat Content, Fatty Acid Composition and Vitamin Content. Int. Dairy J.; 1995; 5, pp. 393-402. [DOI: https://dx.doi.org/10.1016/0958-6946(94)00008-D]

90. Salimei, E.; Varisco, G.; Rosi, F. Major constituents, leptin, and non-protein nitrogen compounds in mares’ colostrum and milk. Reprod. Nutr. Develop.; 2002; 46, pp. 65-72. [DOI: https://dx.doi.org/10.1051/rnd:2002007]

91. Mariani, P.; Summer, A.; Martuzzi, F.; Formaggioni, P.; Sabbioni, A.; Catalano, A.L. Physicochemical properties, gross composition, energy value and nitrogen fractions of Haflinger nursing mare milk throughout 6 lactation months. Anim. Res.; 2001; 50, pp. 415-425. [DOI: https://dx.doi.org/10.1051/animres:2001140]

92. Caroprese, M.; Albenzio, M.; Marino, R.; Muscio, A.; Zezza, T.; Sevi, A. Behavior, Milk Yield, and Milk Composition of Machine and Hand-Milked Murgese Mares. J. Dairy Sci.; 2007; 90, pp. 2773-2777. [DOI: https://dx.doi.org/10.3168/jds.2006-603]

93. Pikul, J.; Wójtowski, J. Fat and cholesterol content and fatty acid composition of mares’ colostrum and milk during five lactation months. Livest. Sci.; 2008; 113, pp. 285-290. [DOI: https://dx.doi.org/10.1016/j.livsci.2007.06.005]

94. Santos, A.S.; Silvestre, A.M. A Study of Lusitano Mare Lactation Curve with Wood’s Model. J. Dairy Sci.; 2008; 91, pp. 760-766. [DOI: https://dx.doi.org/10.3168/jds.2007-0057] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18218764]

95. Cieśla, A.; Palacz, R.; Janiszewska, J.; Skórka, D. Total protein, selected protein fractions and chemical elements in the colostrum and milk of mares. Archiv. Tierzucht.; 2009; 52, pp. 1-6. [DOI: https://dx.doi.org/10.5194/aab-52-1-2009]

96. Summer, A.; Sabbioni, A.; Formaggioni, P.; Mariani, P. Trend in ash and mineral element content of milk from Haflinger nursing mares throughout six lactation months. Livest. Prod. Sci.; 2004; 88, pp. 55-62. [DOI: https://dx.doi.org/10.1016/j.livprodsci.2003.11.002]

97. Doreau, M.; Boulot, S.; Bauchart, D.; Barlet, J.P.; Martin-Rosset, W. Voluntary Intake, Milk Production and Plasma Metabolites in Nursing Mares Fed Two Different Diets. J. Nutr.; 1992; 122, pp. 992-999. [DOI: https://dx.doi.org/10.1093/jn/122.4.992]

98. Bouwman, H.; Van der Schee, W. Composition and production of milk from Dutch warmblooded saddle horse mares. J. Anim. Physiol. Anim. Nutr.; 1978; 40, pp. 39-53. [DOI: https://dx.doi.org/10.1111/j.1439-0396.1978.tb00523.x]

99. Schryver, H.F.; Oftedal, O.T.; Williams, J.; Soderholm, L.V.; Hintz, H.F. Lactation in the Horse: The Mineral Composition of Mare Milk. J. Nutr.; 1986; 116, pp. 2142-2147. [DOI: https://dx.doi.org/10.1093/jn/116.11.2142]

100. Schweigert, F.J.; Gottwald, C. Effect of parturition on levels of vitamins A and E and of β-carotene in plasma and milk of mares. Equine Vet. J.; 1999; 31, pp. 319-323. [DOI: https://dx.doi.org/10.1111/j.2042-3306.1999.tb03824.x]

101. Michaelidou, A.M. Factors influencing nutritional and health profile of milk and milk products. Small Rumin. Res.; 2008; 79, pp. 42-50. [DOI: https://dx.doi.org/10.1016/j.smallrumres.2008.07.007]

102. Vincenzetti, S.; Santini, G.; Polzonetti, V.; Pucciarelli, S.; Klimanova, Y.; Polidori, P. Vitamins in Human and Donkey Milk: Functional and Nutritional Role. Nutrients; 2021; 13, 1509.

103. Salimei, E.; Fantuz, F. Equid milk for human consumption. Int. Dairy J.; 2012; 24, pp. 130-142. [DOI: https://dx.doi.org/10.1016/j.idairyj.2011.11.008]

104. Plakantara, S.; Michaelidou, A.M.; Polychroniadou, A.; Menexes, G.; Alichanidis, E. Nucleotides and nucleosides in ovine and caprine milk during lactation. J. Dairy Sci.; 2010; 93, pp. 2330-2337. [DOI: https://dx.doi.org/10.3168/jds.2009-2836] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20494137]

105. Meyer, A.M.; Reed, J.J.; Neville, T.L.; Thorson, J.F.; Maddock-Carlin, K.R.; Taylor, J.B.; Reynolds, L.P.; Redmer, D.A.; Luther, J.S.; Hammer, C.J. et al. Nutritional plane and selenium supply during gestation affect yield and nutrient composition of colostrum and milk in primiparous ewes. J. Anim. Sci.; 2011; 89, pp. 1627-1639. [DOI: https://dx.doi.org/10.2527/jas.2010-3394] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21521822]

106. Shogo, H.; Masashi, A.; Seiji, K.; Yoshiyuk, T. Effects of parity and litter size on the energy contents and immunoglobulin G concentrations of Awassi ewe colostrum. Turk. J. Vet. Anim. Sci.; 2013; 37, pp. 109-112.

107. Galitsopoulou, A.; Michaelidou, A.M.; Menexes, G.; Alichanidis, E. Polyamine profile in ovine and caprine colostrum and milk. Food Chem.; 2015; 173, pp. 80-85. [DOI: https://dx.doi.org/10.1016/j.foodchem.2014.09.168]

108. Izadi, A.; Rahbarimanesh, A.A.; Mojtahedi, Y.; Mojtahedi, S.Y. Prevalence of enterovirus meningitis in children: Report from a tertiary center. Maedica J. Clin. Med; 2018; 13, pp. 213-216.

109. El-Agamy, E.I. The challenge of cow milk protein allergy. Small Rumin. Res.; 2007; 68, pp. 64-72. [DOI: https://dx.doi.org/10.1016/j.smallrumres.2006.09.016]

110. Monti, G.; Viola, S.; Baro, C.; Cresi, F.; Tovao, P.A.; Moro, G.; Ferrero, M.P.; Conti, A.; Bertino, E. Tolerability of donkey’s milk in 92 highly problematic cow’s milk allergic children. J. Biol. Regul. Homeost. Agents; 2012; 26, pp. 75-82.

111. Vincenzetti, S.; Cammertoni, N.; Rapaccetti, R.; Santini, G.; Klimanova, Y.; Zhang, J.J.; Polidori, P. Nutraceutical and Functional Properties of Camelids’ Milk. Beverages; 2022; 8, 12. [DOI: https://dx.doi.org/10.3390/beverages8010012]

112. Faraz, A.; Waheed, A.; Tauqir, N.A.; Mirza, R.H.; Ishaq, H.M.; Nabeel, M.S. Characteristics and composition of camel (Camelus dromedarius) milk: The white gold of desert. Adv. Anim. Vet. Sci.; 2020; 8, pp. 766-770. [DOI: https://dx.doi.org/10.17582/journal.aavs/2020/8.7.766.770]

113. El-Hatmi, H.; Girardet, J.M.; Gaillard, J.L.; Yahyaoui, M.H.; Attia, H. Characterisation of whey proteins of camel (Camelus dromedarius) milk and colostrum. Small Rumin. Res.; 2007; 70, pp. 267-271. [DOI: https://dx.doi.org/10.1016/j.smallrumres.2006.04.001]

114. Konuspayeva, G.; Faye, B.; Loiseau, G.; Narmuratova, M.; Ivashchenko, A.; Meldebekova, A.; Davletov, S. Physiological change in camel milk composition (Camelus dromedarius) 2: Physico-chemical composition of colostrum. Trop. Anim. Health Prod.; 2010; 42, pp. 501-505. [DOI: https://dx.doi.org/10.1007/s11250-009-9450-4] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19763867]

115. Dell’Orto, V.; Cattaneo, D.; Beretta, E.; Baldi, A.; Savoini, G. Effects of trace element supplementation on milk yield and composition in camels. Int. Dairy, J.; 2010; 10, pp. 873-879. [DOI: https://dx.doi.org/10.1016/S0958-6946(01)00023-1]

116. Izadi, A.; Khedmat, L.; Mojtahedi, S.Y. Nutritional and therapeutic perspectives of camel milk and its protein hydrolysates: A review on versatile biofunctional properties. J. Funct. Foods; 2019; 60, 103441. [DOI: https://dx.doi.org/10.1016/j.jff.2019.103441]