**5. Nutrient functionality**

Nowadays, nutrients have emerged as an important research topic in food and nutrition sciences as they appear to be able to modulate the inflammatory status of humans [70]. Dairy products represent a particularly interesting food type to study in the context of inflammation, mostly because of milk's ability to support the development of the immune system of the newborn, to inhibit bacterial growth, and to provide anti-oxidative and anti-inflammatory protection [71]. Some of these properties might still be maintained in the context of the consumption of dairy products by human adults. Additionally, the ability of milk and milk-products to deliver supplements to the human organism able to modulate the gut microbiota, a key regulator of immunity, is another factor which might help influence immune and inflammatory processes [72, 73].

Recently, reviews by Hsieh et al. [74, 75] have described the effects of different bioactive components of milk and dairy products in preventing low-grade systemic inflammation and in acting as coadjutants in conventional therapies.

In the following sections, after a brief overview structure and function of the immune system, we will focus on the effects of several bioactive compounds found mainly in goat milk and their effects in low-grade systemic inflammatory diseases and immunity.

#### **5.1. Overview of immune system: low-grade systemic inflammation and gut-systemic inflammatory associations**

In ruminants, lipids from meals suffer hydrolyzation and biohydrogenation processes in the rumen, resulting in absorption of saturated fatty acids in the digestive tract. This fact could help explain the higher percentage of saturated fats in meat products obtained from ruminants. Several studies have been conducted in an attempt to determine the fatty acid profile of goat meat [66]. However, the role of certain processes such as biohydrogenation, transition of unsaturated into saturated fatty acids, elongation of fatty acid chains,

The composition of the fat in goat meat and other ruminants differs from that of monogastric animals, having larger amounts of SFA and lower quantities of PUFA, with C18:1 and C18:2 *trans* and *cis* isomers of FA are also present in goat meat. In animals, the main PUFA (C18:2n-6 and C18:3n-3) are obtained from the diet. However, in ruminants, these products suffer biohydrogenation processes in the digestive tract, originating saturated fats as well as other intermediate products, which include *cis* and *trans* C18:1 isomers and C18:2 *trans* isomers, conjugated or unconjugated [67]. While grain feeds are a food source of C18:2n-6, green grass on pastures are richer in C18:3n-3 [68], which is more desirable as it could lead to higher con-

Meat products derived from ruminants are a dietary source of CLA. C18:2 *cis*-9, *trans*-11 is the most frequent isomer of CLA, and is also present in higher amounts in the meat of ruminants fed on pasture than in the meat of ruminants fed with grain. Despite the fact that a fraction of this fatty acid occurs in the rumen, about 70–80% of the acid present in the tissues results from endogenous transformation C18:1 *trans*-11 by the enzyme Δ9 desaturase [69]. Therefore, the difference in CLA concentration in the tissues results mainly from the amount

Nowadays, nutrients have emerged as an important research topic in food and nutrition sciences as they appear to be able to modulate the inflammatory status of humans [70]. Dairy products represent a particularly interesting food type to study in the context of inflammation, mostly because of milk's ability to support the development of the immune system of the newborn, to inhibit bacterial growth, and to provide anti-oxidative and anti-inflammatory protection [71]. Some of these properties might still be maintained in the context of the consumption of dairy products by human adults. Additionally, the ability of milk and milk-products to deliver supplements to the human organism able to modulate the gut microbiota, a key regulator of immunity, is another factor which might help influence immune

Recently, reviews by Hsieh et al. [74, 75] have described the effects of different bioactive components of milk and dairy products in preventing low-grade systemic inflammation

In the following sections, after a brief overview structure and function of the immune system, we will focus on the effects of several bioactive compounds found mainly in goat milk

and their effects in low-grade systemic inflammatory diseases and immunity.

metabolism, and deposition rate are yet to be fully understood.

tents of omega-3 fatty acids in meat products.

of C18:1 *trans*-11 absorbed in the rumen.

**5. Nutrient functionality**

202 Goat Science

and inflammatory processes [72, 73].

and in acting as coadjutants in conventional therapies.

Inflammation is one of the main biological processes involved in response to potentially detrimental stimuli to the body and can be classified as acute or chronic with different processes involved in each of these types. Acute inflammation is an immediate and short-lasting response to irritation, injury, or infection which leads to the activation of mechanisms such as increased blood flow, greater blood vessel permeability, and movement of white blood cells to the affected site. These mechanisms are responsible for the classic signs of inflammation: redness, edema, heat, pain, and decreased function [76]. Chronic inflammation is a long-lasting response to factors such as poor nutrition, stress, environmental toxins, and processes related to aging [76]. These prolong the inflammatory response, leading to destructive reactions which, coupled with inappropriate repair processes, eventually lead to the clinical symptoms of disease [77].

The human immune system possesses innate or nonspecific and adaptive mechanisms that work synergistically to protect the body against injury and infection. Innate immunity constitutes the first line of defence, providing immediate response albeit unspecific response to localized injury or invasion by an infectious agent. Innate immunity is triggered when the inflammasome (a large sensor protein produced by bone marrow) detects a toxic substance and stimulates the production of macrophages to destroy harmful stimuli. Macrophages are able to recognize different types of pathogens and are able to react either by producing several mediators that activate other elements further downstream inflammatory cascade (these include, for instance, toll-like receptors, cytokines, or transcription factors); or by eliminating them directly through a process known as phagocytosis. Innate immunity, however, has a limited duration and is not able to stop all pathogenic stimuli. When overtaxed, the body's adaptive immunity mechanisms are activated [78].

Adaptive immunity or acquired immunity is based in highly specialized responses directed at specific antigens [77]. It can be divided into two types: humoral immunity, in which the B lymphocytes, produced in the bone marrow, generate antibodies targeting specific antigens present in the pathogen in question; and cell-mediated immunity, in which T lymphocytes, matured in the spleen and lymph nodes, recognize antigens present on infected cells and lead to their destruction. Memory cells are also a part of the adaptive immunity response and recognize and react to repeated exposures to specific antigens [77].

When, in the human body, the mechanisms of innate and adaptive immunity are ineffective in eliminating a harmful stimulus, illness occurs. Normal function of the cells is disrupted by processes that include leukocyte proliferation, oxidative reactions, and fibrosis caused by repeated or uncontrolled inflammatory responses. A chronic low-grade inflammatory state as a pathological feature of a wide range of chronic conditions, such as metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), atherosclerosis, cardiovascular diseases (CVD), cancer, neurological diseases, among others, has been recognized [79–81]. The numbers of illnesses, which are related to molecular mediators of inflammation, are large and expanding.

Inflammation constitutes one of the basic mechanisms of the innate immune response. In general, inflammation is a local response to cellular injury that aims not only to eliminate the toxic agents but also to promote repair of damaged tissue [78].

The microbiota present in our bodies also plays an important yet often under looked part in maintaining systemic metabolism and cardiometabolic health [82, 83]. Increasing evidence indicates that a relationship between microbiota, the immune system, and inflammatory processes exists. When chronic disease (such as obesity or processes related to aging) occurs, microbiota loses "richness" altering gene expression diversity and increasing low-grade chronic inflammation [83]. According to Kurashima et al. [84], gastrointestinal tract-microbiota interactions influence immune function by maintaining the function of the mucosal immune system, protecting against invasion by pathogens, and maintaining the integrity of the barriers present in gastrointestinal tract.. The permeability of the walls of the gastrointestinal tract to the lipopolysaccharides (LPS), found on the outer membrane of Gram-negative bacteria, can also induce low-grade systemic inflammation, as LPS is a powerful proinflammatory. In the elderly, a higher count of bacteria that produce LPS in the colon, coupled with a lower amounts of bifidobacteria [85], increases gut permeability, leading to higher amounts of LPS entering the bloodstream, which in turn aggravates inflammation [86]. One of the mechanisms through which LPS may be an important trigger in the development of inflammation and metabolic diseases is an interaction with the Toll-like receptor 4 present on the surface of mononuclear cells [87]. Moreover, in addition to its role in low-grade systemic inflammation, emerging evidence suggests that the gut microbiota can also have an influence in the risk of high-grade autoimmune inflammatory conditions such as type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, and rheumatoid arthritis [88–90].

As we have previously described, the protein present in goat milk is comprised of about 80% caseins and 20% whey proteins. Some of the peptides and proteins in milk present direct biological activity, while other proteins have a latent biological activity, which is activated only upon proteolytic action. For example, the active forms of caprine calmodulin (calcium-binding protein) are the soluble C-terminals obtained as a by-product from the action of chimosin on k-casein during the milk clotting process of cheese-making. These peptides are also important sources of bioactive ACE-inhibitory and anti-hypertensive peptides [95, 96]. Moreover, goat milk possesses other minor proteins including immunoglobulins, lactoferrin, transferring, ferritin, protease peptone, prolactin, and folate-binding protein with biological activity. Furthermore, a variety of naturally formed bioactive peptides have been found in fermented dairy products, such as yoghurt and cheese. The main bioactive peptides of goat milk and its

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Several epidemiological studies have linked dietary intake of milk and dairy foods with a decreased risk of hypertension [97]. Their high mineral content (in calcium, potassium, and magnesium) and certain proteins present in these products (as well as their hydrolysates) have been thought to be involved in the anti-hypertensive effect of these products [98]. Angiotensin-converting enzyme (ACE) is a multifunctional enzyme that acts as one of the main regulators of blood pressure. ACE inhibition, restrain the formation of angiotensin II or block its receptors leading to arteriolar vasodilation and a reduction of total peripheral resistance. Therefore, ACE inhibition is currently considered as one of the best strategies

Inflammation and oxidative stress play an important role in the pathophysiology of hypertension; however, the description of the mechanisms involving all interplays between them is behind the scope of this chapter, nevertheless, we might consider the link between angiotensin II and immune system. Nosalski et al. [100], in a recent revision, state that the bulk of mechanistic model studies clearly indicate that a complex network of interactions between T cells, dendritic cells, monocytes, and B cells may be involved in hypertension. The lack of this immune response has a blunt response to angiotensin II-simulated hypertension and may promote hypertension by potentiating vascular dysfunction. Consequently, hypertension is associated with significant activation of immune and inflammatory systems and shares sev-

Several studies have been done to investigate the bioactivity of goat milk protein hydrolysates and the release of ACE-inhibitory and anti-oxidant peptides with individual proteases such as thermolysin, trypsin, subtilisin, papain, and pepsin or their combinations [95, 103]. Espejo-Carpio et al. [95] and De Gobba et al. [104] identified many casein-derived peptides from hydrolyzed proteins of goats' milk, which were enzymatically liberated by a combination of subtilisin and trypsin. Among them, many peptides contained tyrosine in their sequence and had anti-oxidant and ACE-inhibitory activities. More recently, Ibrahim et al. [105] have shown that ACE-inhibitory peptides can be released from goat milk caseins and whey proteins after gastric pepsin digestion. In their study, they found one peptide from whey

eral functional differences with other immune-mediated diseases [101, 102].

derivatives will be described below.

for hypertension treatment [99].

*6.1.1. Biopeptides that lower blood pressure*

#### **5.2. Food allergy**

Specific immune response also plays a lead role in food allergy. The term "allergy" can be used to define an abnormal adaptive immune response directed against noninfectious environmental substances (allergens), including noninfectious components of certain infectious organisms. After antigen contact, the body responds with an excessive reaction (IgE antibodies, histamine release). The symptoms are dramatic and acute. In allergic disorders, such as some food allergies, these responses are characterized by the involvement of allergenspecific IgE and T helper 2 (TH2) cells that recognize allergen-derived antigens [91].

Recent studies suggest that the consumption of dairy products is inversely associated with lowgrade systemic inflammation [92]. The cross-sectional nature of these studies precludes definite conclusions on the cause-and-effect relation between dairy food consumption and inflammatory outcomes. Considering distinctive proprieties of goat milk, we will summarize some ofthe bioactive compounds present in goat's milk and dairy products and their effects on health.

## **6. Anti-inflammatory effects of goat milk and its derivatives**

#### **6.1. Bioactive peptides**

Bioactive peptides (BP) have been defined as specific protein fragments that have a positive impact on body functions or conditions and may ultimately influence health [93]. According to Atanasova and Ivanova [94], goat milk is as "close to perfect food as possible in nature." As we have previously described, the protein present in goat milk is comprised of about 80% caseins and 20% whey proteins. Some of the peptides and proteins in milk present direct biological activity, while other proteins have a latent biological activity, which is activated only upon proteolytic action. For example, the active forms of caprine calmodulin (calcium-binding protein) are the soluble C-terminals obtained as a by-product from the action of chimosin on k-casein during the milk clotting process of cheese-making. These peptides are also important sources of bioactive ACE-inhibitory and anti-hypertensive peptides [95, 96]. Moreover, goat milk possesses other minor proteins including immunoglobulins, lactoferrin, transferring, ferritin, protease peptone, prolactin, and folate-binding protein with biological activity.

Furthermore, a variety of naturally formed bioactive peptides have been found in fermented dairy products, such as yoghurt and cheese. The main bioactive peptides of goat milk and its derivatives will be described below.

#### *6.1.1. Biopeptides that lower blood pressure*

The microbiota present in our bodies also plays an important yet often under looked part in maintaining systemic metabolism and cardiometabolic health [82, 83]. Increasing evidence indicates that a relationship between microbiota, the immune system, and inflammatory processes exists. When chronic disease (such as obesity or processes related to aging) occurs, microbiota loses "richness" altering gene expression diversity and increasing low-grade chronic inflammation [83]. According to Kurashima et al. [84], gastrointestinal tract-microbiota interactions influence immune function by maintaining the function of the mucosal immune system, protecting against invasion by pathogens, and maintaining the integrity of the barri-

to the lipopolysaccharides (LPS), found on the outer membrane of Gram-negative bacteria, can also induce low-grade systemic inflammation, as LPS is a powerful proinflammatory. In the elderly, a higher count of bacteria that produce LPS in the colon, coupled with a lower amounts of bifidobacteria [85], increases gut permeability, leading to higher amounts of LPS entering the bloodstream, which in turn aggravates inflammation [86]. One of the mechanisms through which LPS may be an important trigger in the development of inflammation and metabolic diseases is an interaction with the Toll-like receptor 4 present on the surface of mononuclear cells [87]. Moreover, in addition to its role in low-grade systemic inflammation, emerging evidence suggests that the gut microbiota can also have an influence in the risk of high-grade autoimmune inflammatory conditions such as type 1 diabetes mellitus, celiac

Specific immune response also plays a lead role in food allergy. The term "allergy" can be used to define an abnormal adaptive immune response directed against noninfectious environmental substances (allergens), including noninfectious components of certain infectious organisms. After antigen contact, the body responds with an excessive reaction (IgE antibodies, histamine release). The symptoms are dramatic and acute. In allergic disorders, such as some food allergies, these responses are characterized by the involvement of allergen-

Recent studies suggest that the consumption of dairy products is inversely associated with lowgrade systemic inflammation [92]. The cross-sectional nature of these studies precludes definite conclusions on the cause-and-effect relation between dairy food consumption and inflammatory outcomes. Considering distinctive proprieties of goat milk, we will summarize some ofthe bioactive compounds present in goat's milk and dairy products and their effects on health.

Bioactive peptides (BP) have been defined as specific protein fragments that have a positive impact on body functions or conditions and may ultimately influence health [93]. According to Atanasova and Ivanova [94], goat milk is as "close to perfect food as possible in nature."

specific IgE and T helper 2 (TH2) cells that recognize allergen-derived antigens [91].

**6. Anti-inflammatory effects of goat milk and its derivatives**

disease, inflammatory bowel disease, and rheumatoid arthritis [88–90].

The permeability of the walls of the gastrointestinal tract

ers present in gastrointestinal tract..

**5.2. Food allergy**

204 Goat Science

**6.1. Bioactive peptides**

Several epidemiological studies have linked dietary intake of milk and dairy foods with a decreased risk of hypertension [97]. Their high mineral content (in calcium, potassium, and magnesium) and certain proteins present in these products (as well as their hydrolysates) have been thought to be involved in the anti-hypertensive effect of these products [98]. Angiotensin-converting enzyme (ACE) is a multifunctional enzyme that acts as one of the main regulators of blood pressure. ACE inhibition, restrain the formation of angiotensin II or block its receptors leading to arteriolar vasodilation and a reduction of total peripheral resistance. Therefore, ACE inhibition is currently considered as one of the best strategies for hypertension treatment [99].

Inflammation and oxidative stress play an important role in the pathophysiology of hypertension; however, the description of the mechanisms involving all interplays between them is behind the scope of this chapter, nevertheless, we might consider the link between angiotensin II and immune system. Nosalski et al. [100], in a recent revision, state that the bulk of mechanistic model studies clearly indicate that a complex network of interactions between T cells, dendritic cells, monocytes, and B cells may be involved in hypertension. The lack of this immune response has a blunt response to angiotensin II-simulated hypertension and may promote hypertension by potentiating vascular dysfunction. Consequently, hypertension is associated with significant activation of immune and inflammatory systems and shares several functional differences with other immune-mediated diseases [101, 102].

Several studies have been done to investigate the bioactivity of goat milk protein hydrolysates and the release of ACE-inhibitory and anti-oxidant peptides with individual proteases such as thermolysin, trypsin, subtilisin, papain, and pepsin or their combinations [95, 103]. Espejo-Carpio et al. [95] and De Gobba et al. [104] identified many casein-derived peptides from hydrolyzed proteins of goats' milk, which were enzymatically liberated by a combination of subtilisin and trypsin. Among them, many peptides contained tyrosine in their sequence and had anti-oxidant and ACE-inhibitory activities. More recently, Ibrahim et al. [105] have shown that ACE-inhibitory peptides can be released from goat milk caseins and whey proteins after gastric pepsin digestion. In their study, they found one peptide from whey β-lactoglobulin, PEQSLACQCL and two peptides from caseins, ARHPHPHLSFM (fragment 96–106 κ-casein), and QSLVYPFTGPI (fragment 56–66 β-casein). These peptides displayed ACE-inhibitory activity that compares favorably with the activity of anti-hypertensive drugs with ACE-inhibitory action. These peptides as well as other hydrophobic peptides additionally exert anti-oxidant and anti-inflammatory activities. Therefore, goat milk and goat whey bioactive peptides present anti-hypertensive activity through inhibition of ACE, but considering all the mechanisms involved in the pathophysiology of hypertension, the existence of multifunctional peptides must be considered [106].

In the same way, caseins seem to be good antimicrobial peptides against Gram-negative bacteria [115]. Esmaeilpour et al. [116] investigated the antimicrobial action of goat milk casein hydrolysates produced by the proteolytic enzymes trypsin and ficin and by combination of both enzymes. The authors obtained fractions with significant antimicrobial activities

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Goat milk lactoferrin demonstrates not only to possess antimicrobial action but also to induce apoptosis in a human cervical cancer cell line [117]. Considering the resemblance with other lactoferrins, goat lactoferrin might be able to present protective activity against other cancers. However, the research in this area is only in its infancy. The mechanisms by which this molecule might exert its activity were recently reviewed by Zhang et al. [118]. These properties of lactoferrin constitute an interesting alternative to chemoprevention, and the currently used anticancer drugs. In addition, its stability through the gastrointestinal tract is beneficial if oral

It seems that intact and hydrolyzed goat whey protein concentrates, blood serum albumin, and skim milk inhibited lymphocyte proliferation in dose-dependent reactions [119]. Su et al. [120, 121] reported that an anticancer bioactive peptide (ACBP) extracted from goat spleens significantly inhibited the growth of human gastric cancer line BGC-823 in vitro in a dosedependent manner. In vivo, ACBP-inhibited human gastric tumor growth in a *xenograft* model with no apparent cytotoxicity to host. The study suggested that ACBP could be a powerful anticancer biological product through induction of cell apoptosis and cell cycle arrest. Furthermore, Yu et al. [122] found using in vitro and in vivo samples that the bioactive peptide-3 (ACBP-3), a peptide isolated from goat liver, presented antitumor properties on gastric cancer stem cells (GCSCs). ACBP-3 was also found to decrease CD44 (+) cells and suppress proliferation of SC (spheroid colonies) cells and their clone-forming capacity alone or in com-

Antioxidant peptides are particularly interesting because they can potentially prevent or delay oxidative stress as well as low-grade systemic inflammation associated chronic diseases [74, 94]. In this sense, milk proteins as well as milk-derived proteins have been considered as potential carriers for the delivery of antioxidant peptides in the gastrointestinal tract, where they may exert direct protective effects by scavenging reactive oxygen species and reducing the oxidative stress [123]. Only a few studies on the antioxidant properties of goat milk protein-derived peptides have been performed. Silva et al. [124] identified three antioxidant peptides in a water extract from a goat cheese-like system made using an extract from *Cynara cardunculus*. Nandhini et al. [125] found that goat milk fermented with *Lactobacillus plantarum* had potent radical scavenging and lipid peroxidation inhibition activity, although they did not identify the active peptides. Li et al. [126] identified antioxidant peptides in a goat's milk casein hydrolysate made using two enzymes (alcalase and pronase), although some of which did not match with the goat casein sequences available in protein databases. De Gobba et al. [104] isolated and identified antioxidant peptides formed from goat's milk protein fractions

against Gram-negative and Gram-positive bacteria.

bination with cisplatin, in a dose-dependent manner [122].

*6.1.3. Cytomodulatory and anticancer peptides*

administration is envisaged.

*6.1.4. Antioxidant peptides*

#### *6.1.2. Antimicrobial peptides*

The antimicrobial activity of milk is mostly attributed to the presence of immunoglobulins and other proteins, such as lactoferrin, lactoperoxidase, and lysozyme. It is generally accepted that the total antibacterial effect in milk is greater than the sum of the individual contributions of immunoglobulin and nonimmunoglobulin defensive proteins. This might be because naturally occurring proteins and peptides act synergistically with peptides that result from metabolization of inactive protein precursors [107]. The proteins present in milk proteins have been proven to act as antimicrobial peptide precursors, thus improving the ability of natural defences to eliminate invading pathogens. Consequently, food proteins can be considered components of nutritional immunity [94]. A paper by Budiarti et al. [108] demonstrates the presence of Alpha-S2 casein in Ethawah goat milk and yoghurt. This protein contains eight bioactive peptides, with different effects, such as anti-osteoporotic or anti-inflammatory effects, and it was not found in cow fresh milk [109, 110]. More recently, Triprisila et al. [111] reported the effect of antimicrobial activity from CSN1S2 protein as a member of casein protein from Ethawah breed goat milk and yoghurt against pathogen Gram-positive bacteria (*Listeria monocytogenes*, *Staphylococcus aureus,* and *Bacillus cereus*) and Gram-negative bacteria (*Escherichia coli*, *Salmonella typhi,* and *Shigella flexneri*). The results of their work showed a greater inhibitory effect on Gram-positive bacteria than on Gram-negative bacteria. They also demonstrated that milk has a higher antimicrobial activity than yoghurt [111].

Goat lactoferrin has been studied after the beneficial effects demonstrated by both human and bovine lactoferrin. The levels of this protein in sheep and goat milk are slightly higher than in cow milk with values of approximately 0.107 ± 19 mg/mL [112]. The concentrations of lactoferrin in goat milk during various stages of lactation have been shown to vary in direct proportion with the number of somatic cells present in the milk samples. These parameters are influenced by a number of physiological processes [112]. Another study, which compared the glycosylation of goat milk lactoferrin with that of other glycoproteins present in human and bovine milk, demonstrated similarities in glycans present in both human and goat milk samples. However, some novel glycans were also identified goat milk, which did not exist in the human milk samples [113]. Considering its high digestibility, immunological properties, and high mineral concentration as well as the similarities between human and goat lactoferrin, goat milk can be considered an attractive candidate for use in infant formula supplementation. Lactoferrin plays an important role in both innate and adaptive immunity responses. Not only pathogens have high affinity toward the iron present in lactoferrin, it also induces changes in leukocytes, involved in innate immune system, by increased activity of NK cells and increasing the phagocytic activity of neutrophils and macrophages [114].

In the same way, caseins seem to be good antimicrobial peptides against Gram-negative bacteria [115]. Esmaeilpour et al. [116] investigated the antimicrobial action of goat milk casein hydrolysates produced by the proteolytic enzymes trypsin and ficin and by combination of both enzymes. The authors obtained fractions with significant antimicrobial activities against Gram-negative and Gram-positive bacteria.

#### *6.1.3. Cytomodulatory and anticancer peptides*

β-lactoglobulin, PEQSLACQCL and two peptides from caseins, ARHPHPHLSFM (fragment 96–106 κ-casein), and QSLVYPFTGPI (fragment 56–66 β-casein). These peptides displayed ACE-inhibitory activity that compares favorably with the activity of anti-hypertensive drugs with ACE-inhibitory action. These peptides as well as other hydrophobic peptides additionally exert anti-oxidant and anti-inflammatory activities. Therefore, goat milk and goat whey bioactive peptides present anti-hypertensive activity through inhibition of ACE, but considering all the mechanisms involved in the pathophysiology of hypertension, the existence

The antimicrobial activity of milk is mostly attributed to the presence of immunoglobulins and other proteins, such as lactoferrin, lactoperoxidase, and lysozyme. It is generally accepted that the total antibacterial effect in milk is greater than the sum of the individual contributions of immunoglobulin and nonimmunoglobulin defensive proteins. This might be because naturally occurring proteins and peptides act synergistically with peptides that result from metabolization of inactive protein precursors [107]. The proteins present in milk proteins have been proven to act as antimicrobial peptide precursors, thus improving the ability of natural defences to eliminate invading pathogens. Consequently, food proteins can be considered components of nutritional immunity [94]. A paper by Budiarti et al. [108] demonstrates the presence of Alpha-S2 casein in Ethawah goat milk and yoghurt. This protein contains eight bioactive peptides, with different effects, such as anti-osteoporotic or anti-inflammatory effects, and it was not found in cow fresh milk [109, 110]. More recently, Triprisila et al. [111] reported the effect of antimicrobial activity from CSN1S2 protein as a member of casein protein from Ethawah breed goat milk and yoghurt against pathogen Gram-positive bacteria (*Listeria monocytogenes*, *Staphylococcus aureus,* and *Bacillus cereus*) and Gram-negative bacteria (*Escherichia coli*, *Salmonella typhi,* and *Shigella flexneri*). The results of their work showed a greater inhibitory effect on Gram-positive bacteria than on Gram-negative bacteria. They

also demonstrated that milk has a higher antimicrobial activity than yoghurt [111].

Goat lactoferrin has been studied after the beneficial effects demonstrated by both human and bovine lactoferrin. The levels of this protein in sheep and goat milk are slightly higher than in cow milk with values of approximately 0.107 ± 19 mg/mL [112]. The concentrations of lactoferrin in goat milk during various stages of lactation have been shown to vary in direct proportion with the number of somatic cells present in the milk samples. These parameters are influenced by a number of physiological processes [112]. Another study, which compared the glycosylation of goat milk lactoferrin with that of other glycoproteins present in human and bovine milk, demonstrated similarities in glycans present in both human and goat milk samples. However, some novel glycans were also identified goat milk, which did not exist in the human milk samples [113]. Considering its high digestibility, immunological properties, and high mineral concentration as well as the similarities between human and goat lactoferrin, goat milk can be considered an attractive candidate for use in infant formula supplementation. Lactoferrin plays an important role in both innate and adaptive immunity responses. Not only pathogens have high affinity toward the iron present in lactoferrin, it also induces changes in leukocytes, involved in innate immune system, by increased activity of NK cells and increasing the phagocytic activity of neutrophils and macrophages [114].

of multifunctional peptides must be considered [106].

*6.1.2. Antimicrobial peptides*

206 Goat Science

Goat milk lactoferrin demonstrates not only to possess antimicrobial action but also to induce apoptosis in a human cervical cancer cell line [117]. Considering the resemblance with other lactoferrins, goat lactoferrin might be able to present protective activity against other cancers. However, the research in this area is only in its infancy. The mechanisms by which this molecule might exert its activity were recently reviewed by Zhang et al. [118]. These properties of lactoferrin constitute an interesting alternative to chemoprevention, and the currently used anticancer drugs. In addition, its stability through the gastrointestinal tract is beneficial if oral administration is envisaged.

It seems that intact and hydrolyzed goat whey protein concentrates, blood serum albumin, and skim milk inhibited lymphocyte proliferation in dose-dependent reactions [119]. Su et al. [120, 121] reported that an anticancer bioactive peptide (ACBP) extracted from goat spleens significantly inhibited the growth of human gastric cancer line BGC-823 in vitro in a dosedependent manner. In vivo, ACBP-inhibited human gastric tumor growth in a *xenograft* model with no apparent cytotoxicity to host. The study suggested that ACBP could be a powerful anticancer biological product through induction of cell apoptosis and cell cycle arrest. Furthermore, Yu et al. [122] found using in vitro and in vivo samples that the bioactive peptide-3 (ACBP-3), a peptide isolated from goat liver, presented antitumor properties on gastric cancer stem cells (GCSCs). ACBP-3 was also found to decrease CD44 (+) cells and suppress proliferation of SC (spheroid colonies) cells and their clone-forming capacity alone or in combination with cisplatin, in a dose-dependent manner [122].

#### *6.1.4. Antioxidant peptides*

Antioxidant peptides are particularly interesting because they can potentially prevent or delay oxidative stress as well as low-grade systemic inflammation associated chronic diseases [74, 94]. In this sense, milk proteins as well as milk-derived proteins have been considered as potential carriers for the delivery of antioxidant peptides in the gastrointestinal tract, where they may exert direct protective effects by scavenging reactive oxygen species and reducing the oxidative stress [123]. Only a few studies on the antioxidant properties of goat milk protein-derived peptides have been performed. Silva et al. [124] identified three antioxidant peptides in a water extract from a goat cheese-like system made using an extract from *Cynara cardunculus*. Nandhini et al. [125] found that goat milk fermented with *Lactobacillus plantarum* had potent radical scavenging and lipid peroxidation inhibition activity, although they did not identify the active peptides. Li et al. [126] identified antioxidant peptides in a goat's milk casein hydrolysate made using two enzymes (alcalase and pronase), although some of which did not match with the goat casein sequences available in protein databases. De Gobba et al. [104] isolated and identified antioxidant peptides formed from goat's milk protein fractions by enzymatic hydrolysis using trypsin and subtilisin, both individually and in combination. They found hydrolysates with high radical scavenging activity attributed to the presence of short peptides. Furthermore, an abundance of tyrosine in novel casein-derived peptides seems to play an important role in the radical scavenging capacity of the peptides. Also, peptide fractions with a high abundance of phenylalanine showed the ability to prevent the formation of secondary lipid oxidation products.

been suggested to be mediated by interaction with opioid receptors [140]. Also, this peptide, another β-casein fragment (identified in commercial yoghurt), whey proteins hydrolysates and β-lactorphin have been reported to stimulate the expression of mucin Muc2 and Muc3 genes [141, 142]. Additional gut-protective effects, exerted by a cheese whey protein diet and a diet supplemented with Thr, Ser, Cys, and Pro residues, have been demonstrated by Sprong et al. in colitis and chemical-induced ulcerative gastric lesions [143, 144]. The enhancement of the mucosal immune response is also a dietary modulating strategy of the defense systems protecting the gastrointestinal tract. Kitamura and Otani showed that ingestion of cakes enriched with casein phosphopeptides increased fecal IgA content in healthy indi-

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Imbalances in both oxidative and inflammatory status are involved in the etiology of several human chronic diseases that affect the digestive tract, such as ulcerative colitis and Crohn's disease. This has encouraged the search of natural preventive treatments against these imbal-

The minor constituents of goat milk, namely lysozyme and transforming growth factor-β (TGF-β), seem to offer additional protection against intestinal cell damage/inflammation [147]. Several authors have shown that oral administration of TGF-β has anti-inflammatory effects at the intestinal level in animal models of colitis [148]. Schiffrin et al. showed that TGF-β administration lowered leucocytes in the blood stream, as well as the levels of the acute phase reactants fibrinogen and orosomucoid. Colonic weight and thickness and mRNA synthesis for IFN-γ production were also reduced. Finally, TGF-β supplementation also increased mucin-2 production in the caecum and normalized muscle proteolytic activity [149]. Goat milk has a much higher level of growth factor activity than that of cow milk [140], thus mak-

Cow's milk allergy is a common disease of infancy and childhood, and its prevalence is about 2.5% during the first 3 years of life [151]. It is an IgE-mediated allergy, meaning that body produces IgE antibodies against certain protein (allergens) in cow milk. Repeated ingestions of milk lead to identification of antigens present in milk by these IgE antibodies, triggering an immune response that causes symptoms such as eczema, respiratory symptoms (wheezing or asthma), gastrointestinal symptoms, or anaphylaxis. Some proteins, namely αS1-casein and β-lactoglobulin (the structures and composition of which vary between animal species) are known to be important allergens in cow's milk allergy. The allergy-causing properties of β-lactoglobulin can be partially eliminated by heat denaturation [11]. However, caseins maintain the capability of binding to lgEs even after a strong denaturing process [39]. Because the content of αS1-casein is low in goat milk, it is plausible that for children with high sensitivity to αs1-casein of cow milk, goat's milk could be considered an alternative source of milk. More recently, several studies report extensive cross-reactivity between cow and goat milk, caused by cow milk-specific IgE antibodies [152]. Because of the cross reactivity, all scientific reports dissuade persons with cow milk allergy to ingest goat milk. Interestingly, allergy to goat's and sheep's milk without allergy to cow's milk has been reported [153]. However,

viduals, suggesting a positive effect on mucosal immunity [145].

ing goat milk a possible nutraceutical for gastrointestinal disorders [150].

ances and, consequently, against disease [146].

*6.1.6. Prevention of milk allergy*

#### *6.1.5. Immunomodulatory/anti-inflammatory peptides*

As stated above, some peptides can present more than one function. Antimicrobial action of goat lactoferrin and some goat caseins is not only antimicrobial but also acts in the immune system.

A proline-rich polypeptide complex, named colostrinin (CLN), was isolated from ovine colostrum [127]. Cell culture and in vivo studies have shown colostrinin to have anti-inflammatory and antioxidant properties. It also was found to play a regulatory role in growth and differentiation of lymphocytes. Colostrinin also inhibits pathological conditions associated with β-amyloid aggregation in neurons [128, 129]. The CLN complex was also found to present neuroprotective activity, inhibiting nerve cell apoptosis induced by the deposition of toxic amyloid [130]. Colostrinin improves learning and memory in rats, delays the progression of dementia, and loss of long-term memory in aging animals [131, 132]. In humans, positive results of preliminary clinical trials have been found [133, 134].

Zhang et al. [135] also found DPP-IV-inhibitory peptides in goat milk casein-derived hydrolyzed with a combination of trypsin and chymotrypsin thus conferring moderate antidiabetic properties to goat's peptides.

The works of Jirillo et al. [136] recently investigated the effects of goat milk on human blood cells in terms of cytokine release and nitric oxide (NO). The results of their work demonstrated that goat milk was able to trigger cytokine production (IL-10, TNF-α, and IL-6) as well as activate NO release from blood cells. It is well known that NO release can be useful in the prevention of cardiovascular disease being a strong vasodilator and an effective antimicrobial agent. Furthermore, NO possesses other antiatherogenic activities, such as (i) inhibition of influx of atherogenic monocytes and LDL into the wall of arteries; (ii) inhibition of adhesion to the vascular wall of proliferating smooth muscle cells; (iii) inhibition of platelet aggregation; (iv) inhibition of the expression of genes involved in atherogenesis [137]. Goat milk can be helpful in maintaining inflammatory homeostasis by stimulating production of multiple cytokines with a variety of effects, such as TNF-α (a proinflammatory cytokine), IL-6 (an acute phase reactant and growth factor for B cells), and IL-10 (an anti-inflammatory cytokine) [138].

Nowadays, the modulator effect of the diet on the gastrointestinal tract functions has been accepted as essential for maintaining and improving the general health of the host [139]. Dairy proteins, hydrolysates, and peptides have been demonstrated to transform the dynamics of mucus mainly via influencing the mucin secretion and expression and the number of goblet cells. The β-casein-derived peptide β-casomorphin 7 produced the same effects that have been suggested to be mediated by interaction with opioid receptors [140]. Also, this peptide, another β-casein fragment (identified in commercial yoghurt), whey proteins hydrolysates and β-lactorphin have been reported to stimulate the expression of mucin Muc2 and Muc3 genes [141, 142]. Additional gut-protective effects, exerted by a cheese whey protein diet and a diet supplemented with Thr, Ser, Cys, and Pro residues, have been demonstrated by Sprong et al. in colitis and chemical-induced ulcerative gastric lesions [143, 144]. The enhancement of the mucosal immune response is also a dietary modulating strategy of the defense systems protecting the gastrointestinal tract. Kitamura and Otani showed that ingestion of cakes enriched with casein phosphopeptides increased fecal IgA content in healthy individuals, suggesting a positive effect on mucosal immunity [145].

Imbalances in both oxidative and inflammatory status are involved in the etiology of several human chronic diseases that affect the digestive tract, such as ulcerative colitis and Crohn's disease. This has encouraged the search of natural preventive treatments against these imbalances and, consequently, against disease [146].

The minor constituents of goat milk, namely lysozyme and transforming growth factor-β (TGF-β), seem to offer additional protection against intestinal cell damage/inflammation [147]. Several authors have shown that oral administration of TGF-β has anti-inflammatory effects at the intestinal level in animal models of colitis [148]. Schiffrin et al. showed that TGF-β administration lowered leucocytes in the blood stream, as well as the levels of the acute phase reactants fibrinogen and orosomucoid. Colonic weight and thickness and mRNA synthesis for IFN-γ production were also reduced. Finally, TGF-β supplementation also increased mucin-2 production in the caecum and normalized muscle proteolytic activity [149]. Goat milk has a much higher level of growth factor activity than that of cow milk [140], thus making goat milk a possible nutraceutical for gastrointestinal disorders [150].

#### *6.1.6. Prevention of milk allergy*

by enzymatic hydrolysis using trypsin and subtilisin, both individually and in combination. They found hydrolysates with high radical scavenging activity attributed to the presence of short peptides. Furthermore, an abundance of tyrosine in novel casein-derived peptides seems to play an important role in the radical scavenging capacity of the peptides. Also, peptide fractions with a high abundance of phenylalanine showed the ability to prevent the for-

As stated above, some peptides can present more than one function. Antimicrobial action of goat lactoferrin and some goat caseins is not only antimicrobial but also acts in the immune

A proline-rich polypeptide complex, named colostrinin (CLN), was isolated from ovine colostrum [127]. Cell culture and in vivo studies have shown colostrinin to have anti-inflammatory and antioxidant properties. It also was found to play a regulatory role in growth and differentiation of lymphocytes. Colostrinin also inhibits pathological conditions associated with β-amyloid aggregation in neurons [128, 129]. The CLN complex was also found to present neuroprotective activity, inhibiting nerve cell apoptosis induced by the deposition of toxic amyloid [130]. Colostrinin improves learning and memory in rats, delays the progression of dementia, and loss of long-term memory in aging animals [131, 132]. In humans, positive

Zhang et al. [135] also found DPP-IV-inhibitory peptides in goat milk casein-derived hydrolyzed with a combination of trypsin and chymotrypsin thus conferring moderate antidiabetic

The works of Jirillo et al. [136] recently investigated the effects of goat milk on human blood cells in terms of cytokine release and nitric oxide (NO). The results of their work demonstrated that goat milk was able to trigger cytokine production (IL-10, TNF-α, and IL-6) as well as activate NO release from blood cells. It is well known that NO release can be useful in the prevention of cardiovascular disease being a strong vasodilator and an effective antimicrobial agent. Furthermore, NO possesses other antiatherogenic activities, such as (i) inhibition of influx of atherogenic monocytes and LDL into the wall of arteries; (ii) inhibition of adhesion to the vascular wall of proliferating smooth muscle cells; (iii) inhibition of platelet aggregation; (iv) inhibition of the expression of genes involved in atherogenesis [137]. Goat milk can be helpful in maintaining inflammatory homeostasis by stimulating production of multiple cytokines with a variety of effects, such as TNF-α (a proinflammatory cytokine), IL-6 (an acute phase reactant and growth factor for B cells), and IL-10 (an anti-inflammatory

Nowadays, the modulator effect of the diet on the gastrointestinal tract functions has been accepted as essential for maintaining and improving the general health of the host [139]. Dairy proteins, hydrolysates, and peptides have been demonstrated to transform the dynamics of mucus mainly via influencing the mucin secretion and expression and the number of goblet cells. The β-casein-derived peptide β-casomorphin 7 produced the same effects that have

mation of secondary lipid oxidation products.

system.

208 Goat Science

properties to goat's peptides.

cytokine) [138].

*6.1.5. Immunomodulatory/anti-inflammatory peptides*

results of preliminary clinical trials have been found [133, 134].

Cow's milk allergy is a common disease of infancy and childhood, and its prevalence is about 2.5% during the first 3 years of life [151]. It is an IgE-mediated allergy, meaning that body produces IgE antibodies against certain protein (allergens) in cow milk. Repeated ingestions of milk lead to identification of antigens present in milk by these IgE antibodies, triggering an immune response that causes symptoms such as eczema, respiratory symptoms (wheezing or asthma), gastrointestinal symptoms, or anaphylaxis. Some proteins, namely αS1-casein and β-lactoglobulin (the structures and composition of which vary between animal species) are known to be important allergens in cow's milk allergy. The allergy-causing properties of β-lactoglobulin can be partially eliminated by heat denaturation [11]. However, caseins maintain the capability of binding to lgEs even after a strong denaturing process [39]. Because the content of αS1-casein is low in goat milk, it is plausible that for children with high sensitivity to αs1-casein of cow milk, goat's milk could be considered an alternative source of milk. More recently, several studies report extensive cross-reactivity between cow and goat milk, caused by cow milk-specific IgE antibodies [152]. Because of the cross reactivity, all scientific reports dissuade persons with cow milk allergy to ingest goat milk. Interestingly, allergy to goat's and sheep's milk without allergy to cow's milk has been reported [153]. However, this food allergy develops later in childhood and not in early childhood as cow's milk proteins allergy, and all the children tolerated cow's milk. Cow milk proteins have been shown to have higher binding capacity to lgE and lgG than proteins present in goat milk. In animal models, cow milk has induced higher lymphocyte proliferation, IL-4 production, histamine secretion, and IgG production [154], which indicates a more exacerbated allergic response.

described, caprine milk has more fat globules than cow milk, with a smaller size. These characteristics are important, as they increase the surface area of the globules in contact with pancreatic lipase in the intestinal tract. This allows for better digestibility and a more efficient lipid metabolism, when compared with cow milk fat [155]. Goat milk is therefore recommended

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211

There are several lipid components that have bioactive functions, such as short- and mediumchain fatty acids (MCT), phospholipids, cholesterol, gangliosides, and glycolipids, etc. Goat milk has a relatively high amount of saturated fatty acids (SFAs; 53–72%) and a relatively low content of polyunsaturated fatty acids (PUFAs; 2–6% of fatty acid composition); the remain-

**Table 3** demonstrates that the fatty acid content of goat milk differs from that of cow milk, the former having much higher amounts of butyric (C4:0), caproic (C6:0), caprylic (C8:0), capric (C10:0), lauric (C12:0), myristic (C14:0), palmitic (C16:0), linoleic (C18:2) acids, but lower stearic (C18:0) and oleic acids (C18:1) contents. Three of the medium-chain fatty acids (caproic, caprylic, and capric) represent 15% of the total fatty acid content, compared to only

According to Ceballos et al. [26], goat milk also has higher proportions of n-3 and n-6 polyunsaturated fatty acids (PUFA) as well as conjugated linoleic acid (CLA). The work of De La Fuente et al. [157] demonstrates that flock, day of testing within each flock, lactation stage, age of ewe, and season had a significant effect on fatty acid content in dairy sheep milk. They also show that the three quantitatively most important sources of variation in fatty acid content were flock, season, and circumstances of testing within each flock. The most important variations related to testing within each flock and season effects occurred in rumenic (CLA) and linolenic acids. These two fatty acids were higher in spring-summer than in winter. Moreover, lactation stage and age of ewe had a significant effect on some FA. As the age of ewe increased, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) decreased and sum of short-chain saturated fatty acids (C4 to C10, SCFA), sum of medium-chain saturated fatty acids (C12–C15, MCFA) increased. Despite the fact that the work of De La Fuente

et al. [157] focused on ovine milk, the same factors can also influence goat milk.

Conjugated linoleic acids (CLA) are naturally occurring isomers of linoleic acid. They are a result of biohydrogenation in the rumen of ruminants and influence the concentration of fatty acids in milk [29]. The conjugated linoleic acid found in goat milk fat comes from two sources: ruminal biohydrogenation of linoleic acid (C18:2 n-6) that leads first to vaccenic (trans-11 C18:1) and finally, to stearic acid (C18:0); and synthesis from trans-11 C18:1, an intermediate product of biohydrogenation of unsaturated FA, in animal tissues. Therefore, the conjugated linoleic acid contents in food products derived from ruminants are derived from incomplete biohydrogenation of unsaturated fatty acids in the rumen. Ruminal biohydrogenation, combined with the mammary lipogenic and ∆-9 desaturation pathways, modifies the profile of dietary fatty acids and consequently milk composition [29]. Food products obtained from ruminants, such as milk, cheese, and meat, contain more CLAs than foods

ing fat is constituted by monounsaturated fatty acids (MUFAs) [156].

for infants, elderly, and convalescing people.

5% in cow milk [12].

of nonruminant origin [158].

As described above, peptides present in goat products have been claimed to be active on a wide spectrum of biological functions or diseases, including blood pressure and metabolic risk factors (coagulation, obesity, lipoprotein metabolism, peroxidation, gut and neurological functions, immunity, and cancer). **Figure 1** presents a schematic representation of these different active biological functions.

#### **6.2. Bioactive lipid components of goat milk**

Milk lipids have a complex composition, consisting of a variety of bioactive substances with various health effects. Lipids in milk are organized in unique structures: milk fat globules. These structures are important in delivering essential nutrients to the neonate, as they increase bioavailability of lipids. Fat globules have also recently an object of interest in food science, namely their use as a method of delivering other beneficial bioactive nutrients. As previously

**Figure 1.** Schematic representation of the wide spectrum of biological functions of caprine biopeptides.

described, caprine milk has more fat globules than cow milk, with a smaller size. These characteristics are important, as they increase the surface area of the globules in contact with pancreatic lipase in the intestinal tract. This allows for better digestibility and a more efficient lipid metabolism, when compared with cow milk fat [155]. Goat milk is therefore recommended for infants, elderly, and convalescing people.

this food allergy develops later in childhood and not in early childhood as cow's milk proteins allergy, and all the children tolerated cow's milk. Cow milk proteins have been shown to have higher binding capacity to lgE and lgG than proteins present in goat milk. In animal models, cow milk has induced higher lymphocyte proliferation, IL-4 production, histamine secretion,

As described above, peptides present in goat products have been claimed to be active on a wide spectrum of biological functions or diseases, including blood pressure and metabolic risk factors (coagulation, obesity, lipoprotein metabolism, peroxidation, gut and neurological functions, immunity, and cancer). **Figure 1** presents a schematic representation of these different

Milk lipids have a complex composition, consisting of a variety of bioactive substances with various health effects. Lipids in milk are organized in unique structures: milk fat globules. These structures are important in delivering essential nutrients to the neonate, as they increase bioavailability of lipids. Fat globules have also recently an object of interest in food science, namely their use as a method of delivering other beneficial bioactive nutrients. As previously

and IgG production [154], which indicates a more exacerbated allergic response.

**Figure 1.** Schematic representation of the wide spectrum of biological functions of caprine biopeptides.

active biological functions.

210 Goat Science

**6.2. Bioactive lipid components of goat milk**

There are several lipid components that have bioactive functions, such as short- and mediumchain fatty acids (MCT), phospholipids, cholesterol, gangliosides, and glycolipids, etc. Goat milk has a relatively high amount of saturated fatty acids (SFAs; 53–72%) and a relatively low content of polyunsaturated fatty acids (PUFAs; 2–6% of fatty acid composition); the remaining fat is constituted by monounsaturated fatty acids (MUFAs) [156].

**Table 3** demonstrates that the fatty acid content of goat milk differs from that of cow milk, the former having much higher amounts of butyric (C4:0), caproic (C6:0), caprylic (C8:0), capric (C10:0), lauric (C12:0), myristic (C14:0), palmitic (C16:0), linoleic (C18:2) acids, but lower stearic (C18:0) and oleic acids (C18:1) contents. Three of the medium-chain fatty acids (caproic, caprylic, and capric) represent 15% of the total fatty acid content, compared to only 5% in cow milk [12].

According to Ceballos et al. [26], goat milk also has higher proportions of n-3 and n-6 polyunsaturated fatty acids (PUFA) as well as conjugated linoleic acid (CLA). The work of De La Fuente et al. [157] demonstrates that flock, day of testing within each flock, lactation stage, age of ewe, and season had a significant effect on fatty acid content in dairy sheep milk. They also show that the three quantitatively most important sources of variation in fatty acid content were flock, season, and circumstances of testing within each flock. The most important variations related to testing within each flock and season effects occurred in rumenic (CLA) and linolenic acids. These two fatty acids were higher in spring-summer than in winter. Moreover, lactation stage and age of ewe had a significant effect on some FA. As the age of ewe increased, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) decreased and sum of short-chain saturated fatty acids (C4 to C10, SCFA), sum of medium-chain saturated fatty acids (C12–C15, MCFA) increased. Despite the fact that the work of De La Fuente et al. [157] focused on ovine milk, the same factors can also influence goat milk.

Conjugated linoleic acids (CLA) are naturally occurring isomers of linoleic acid. They are a result of biohydrogenation in the rumen of ruminants and influence the concentration of fatty acids in milk [29]. The conjugated linoleic acid found in goat milk fat comes from two sources: ruminal biohydrogenation of linoleic acid (C18:2 n-6) that leads first to vaccenic (trans-11 C18:1) and finally, to stearic acid (C18:0); and synthesis from trans-11 C18:1, an intermediate product of biohydrogenation of unsaturated FA, in animal tissues. Therefore, the conjugated linoleic acid contents in food products derived from ruminants are derived from incomplete biohydrogenation of unsaturated fatty acids in the rumen. Ruminal biohydrogenation, combined with the mammary lipogenic and ∆-9 desaturation pathways, modifies the profile of dietary fatty acids and consequently milk composition [29]. Food products obtained from ruminants, such as milk, cheese, and meat, contain more CLAs than foods of nonruminant origin [158].

Many researchers have investigated the effect of goat milk fatty acids in human research. The short- and medium-chain fatty acids in goat milk exhibit several bioactive effects in digestion, lipid metabolism, and treatment of lipid malabsorption syndromes. The important bioactive lipid components in goat milk have been explored in a recent review by Park [140].

Furthermore, sphingolipids and their digestion products, ceramides and sphingosines, have been associated with a variety of health benefits, namely anti-carcinogenic effects, immune regulation, prevention of food-borne infections, and reduction of serum LDL cholesterol [170]. As it was described above, milk is not only the main source of energy for the neonate of each species, but its components also have the potential to influence many aspects of physiology from the central nervous system to the immune system, while also exerting both antibacterial

Nutritional and Health Profile of Goat Products: Focus on Health Benefits of Goat Milk

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213

Lactose is the major carbohydrate in milk with an average content of 4.1 g/100 mL in goat milk [11]. This disaccharide is a valuable nutrient because it favors the intestinal absorption of calcium, magnesium, and human milk oligosaccharides phosphorus, and the utilization of vitamin C. On the other hand, milk oligosaccharides possess prebiotic and anti-infective properties. The amount of oligosaccharides in caprine milk ranges from 250 to 300 mg/ml. Sialic acid, a general name for N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid 355 (Neu5Gc), exists in many of these oligosaccharides and is important in promoting the development of the brain during infancy, among other beneficial effects [140]. Although goat milk is the richest source of oligosaccharides among the different types of milk from farm animals, its content is significantly lower compared to human milk (21–24 g/l for human colostrum; 12–13 g/l for mature human milk) [11]. However, from a structural point of view, among the oligosaccharides found in different types of milk, goat milk oligosaccharides are

While a wide range of biological functions has been attributed to human milk oligosaccharides, less information is available regarding the biological activities of ruminant's milk oligosaccharides and complex oligosaccharides. In short, human milk oligosaccharides are considered to have mainly prebiotic and anti-infectious properties, thus being beneficial for humans, especially for the human-milk-fed neonate [172]. Goat milk seems to be a very appealing candidate for a natural source of human-like oligosaccharides due to its concentration and structure. However, research data on the bioactive oligosaccharides of goat milk is still scarce.

Based on the above, goat oligosaccharides have gained lately much attention as potential nutritional supplements or therapeutic agents. Therefore, they have been used in a number

A healthy gut microbiota, composed primarily of bifidobacteria and lactobacilli, which are bacteria presenting saccharolytic activity, has been linked with multiple health benefits. This can be explained by the interactions of intestinal bacteria with metabolic processes and the endocrine and immune systems of infants and adults. Intestinal colonization with a balanced microbiota is of major importance for the appropriate development of the immune system, and there is an enormous scientific and commercial interest in modifying the microbiota for health promotion [173]. As the gut is sterile at birth, it is an organ sensitive to environmental

and antiviral effects.

**6.3. Biological activity of oligosaccharides**

the most similar to human milk oligosaccharides [171].

of studies in order to evaluate their health-promoting effects.

*6.3.1. Prebiotic and antipathogenic activity*

Short- and medium-chain fatty acids are transported directly from the intestine to portal circulation after hydrolysis of the parent triglyceride, without undergoing resynthesis of triacylglycerols. Therefore, they can be used for instant energy production for muscles, heart, liver, kidneys, blood platelets, and the nervous system and are not available for adipose formation. The consumption of a wide range of fermentable carbohydrates can lead to the synthesis of butyric acid, a well-known modulator of genetic regulation, by endogenous microbiota in the lower intestine. This fatty acid is also present in milk, and its properties have prompted various investigators to target this mechanism in an attempt to reduce cancer risk [159]. Butyric acid, by binding short-chain fatty acid receptors, also manages to reduce the inflammatory response in the intestine [160].

Capric and caprylic acids have similar antimicrobial effects. Caprylic acid lowers salmonella infection in chickens [161] and both caprylic and capric acid have antiviral activity. Monocaprin, their monoglyceride form, has been shown *in vivo* to possess antiviral activity against infection by retrovirus [162]. The release of lauric acid in the stomach may have direct antimicrobial activities toward *Helicobacter pylori* [163]. The above fatty acids do not increase blood lipid levels, and they do not contribute to the risk of obesity. Palmitic acid has shown to improve intestinal absorption not just of the palmitic acid but calcium as well as stimulated the expression and activities of the transcription coactivator PGC-1b and by so doing promoted the transcriptional regulation of biosynthesis of lipoproteins from the liver [164, 165].

Milk fat contains essential fatty acids (EFAs) that are not synthesized by the body and therefore have to be supplied with food. Polyunsaturated fatty acids have beneficial health effects by increasing the synthesis of eicosanoids, molecules that regulate cardiovascular function, blood pressure, coagulation, plasma triacylglycerol concentrations, immune response, inflammation, neoplastic proliferation, hormone, and neurotransmitter activity, gene expression, renal function, and pain. Eicosanoids boost immunity, lower cholesterol levels in peripheral blood by stimulating lipid transport, thus reducing the risk of ischemic heart disease [166]. Fatty acids from the n-3 family, commonly known as omega-3 fatty acids, can be useful in the management of inflammatory diseases, such as rheumatoid arthritis, as well as in decreasing symptoms of mental disorders and dementia. DHA was found to be effective in late-stage Alzheimer's disease [167].

Conjugated linoleic acid was recognized as having anti-oxidative and anti-carcinogenic properties in animal model studies [158]. CLA has important functional properties, such as inhibiting the growth of skin, gastric, breast, and colorectal cancer cells [168]. The *cis*-9, *trans*-11 isomer shows the biological activities, but other isomers seem to have beneficial effects as well, such as *trans*-10, *cis*-12, which is believed to prevent the development of obesity [169]. CLA helps prevent osteoporosis, reduces blood sugar levels, boosts immune system function, lowers total cholesterol and LDL cholesterol levels, and improves the LDL/HDL ratio in the blood plasma, thus contributing to the prevention of ischemic heart disease and atherosclerosis [170].

Furthermore, sphingolipids and their digestion products, ceramides and sphingosines, have been associated with a variety of health benefits, namely anti-carcinogenic effects, immune regulation, prevention of food-borne infections, and reduction of serum LDL cholesterol [170].

As it was described above, milk is not only the main source of energy for the neonate of each species, but its components also have the potential to influence many aspects of physiology from the central nervous system to the immune system, while also exerting both antibacterial and antiviral effects.

#### **6.3. Biological activity of oligosaccharides**

Many researchers have investigated the effect of goat milk fatty acids in human research. The short- and medium-chain fatty acids in goat milk exhibit several bioactive effects in digestion, lipid metabolism, and treatment of lipid malabsorption syndromes. The important bioactive lipid components in goat milk have been explored in a recent review by Park [140].

Short- and medium-chain fatty acids are transported directly from the intestine to portal circulation after hydrolysis of the parent triglyceride, without undergoing resynthesis of triacylglycerols. Therefore, they can be used for instant energy production for muscles, heart, liver, kidneys, blood platelets, and the nervous system and are not available for adipose formation. The consumption of a wide range of fermentable carbohydrates can lead to the synthesis of butyric acid, a well-known modulator of genetic regulation, by endogenous microbiota in the lower intestine. This fatty acid is also present in milk, and its properties have prompted various investigators to target this mechanism in an attempt to reduce cancer risk [159]. Butyric acid, by binding short-chain fatty acid receptors, also manages to reduce the inflam-

Capric and caprylic acids have similar antimicrobial effects. Caprylic acid lowers salmonella infection in chickens [161] and both caprylic and capric acid have antiviral activity. Monocaprin, their monoglyceride form, has been shown *in vivo* to possess antiviral activity against infection by retrovirus [162]. The release of lauric acid in the stomach may have direct antimicrobial activities toward *Helicobacter pylori* [163]. The above fatty acids do not increase blood lipid levels, and they do not contribute to the risk of obesity. Palmitic acid has shown to improve intestinal absorption not just of the palmitic acid but calcium as well as stimulated the expression and activities of the transcription coactivator PGC-1b and by so doing promoted the transcriptional regulation of biosynthesis of lipoproteins from the liver [164, 165]. Milk fat contains essential fatty acids (EFAs) that are not synthesized by the body and therefore have to be supplied with food. Polyunsaturated fatty acids have beneficial health effects by increasing the synthesis of eicosanoids, molecules that regulate cardiovascular function, blood pressure, coagulation, plasma triacylglycerol concentrations, immune response, inflammation, neoplastic proliferation, hormone, and neurotransmitter activity, gene expression, renal function, and pain. Eicosanoids boost immunity, lower cholesterol levels in peripheral blood by stimulating lipid transport, thus reducing the risk of ischemic heart disease [166]. Fatty acids from the n-3 family, commonly known as omega-3 fatty acids, can be useful in the management of inflammatory diseases, such as rheumatoid arthritis, as well as in decreasing symptoms of mental disorders and dementia. DHA was found to be effective

Conjugated linoleic acid was recognized as having anti-oxidative and anti-carcinogenic properties in animal model studies [158]. CLA has important functional properties, such as inhibiting the growth of skin, gastric, breast, and colorectal cancer cells [168]. The *cis*-9, *trans*-11 isomer shows the biological activities, but other isomers seem to have beneficial effects as well, such as *trans*-10, *cis*-12, which is believed to prevent the development of obesity [169]. CLA helps prevent osteoporosis, reduces blood sugar levels, boosts immune system function, lowers total cholesterol and LDL cholesterol levels, and improves the LDL/HDL ratio in the blood plasma, thus contributing to the prevention of ischemic heart disease and atherosclerosis [170].

matory response in the intestine [160].

212 Goat Science

in late-stage Alzheimer's disease [167].

Lactose is the major carbohydrate in milk with an average content of 4.1 g/100 mL in goat milk [11]. This disaccharide is a valuable nutrient because it favors the intestinal absorption of calcium, magnesium, and human milk oligosaccharides phosphorus, and the utilization of vitamin C. On the other hand, milk oligosaccharides possess prebiotic and anti-infective properties. The amount of oligosaccharides in caprine milk ranges from 250 to 300 mg/ml. Sialic acid, a general name for N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid 355 (Neu5Gc), exists in many of these oligosaccharides and is important in promoting the development of the brain during infancy, among other beneficial effects [140]. Although goat milk is the richest source of oligosaccharides among the different types of milk from farm animals, its content is significantly lower compared to human milk (21–24 g/l for human colostrum; 12–13 g/l for mature human milk) [11]. However, from a structural point of view, among the oligosaccharides found in different types of milk, goat milk oligosaccharides are the most similar to human milk oligosaccharides [171].

While a wide range of biological functions has been attributed to human milk oligosaccharides, less information is available regarding the biological activities of ruminant's milk oligosaccharides and complex oligosaccharides. In short, human milk oligosaccharides are considered to have mainly prebiotic and anti-infectious properties, thus being beneficial for humans, especially for the human-milk-fed neonate [172]. Goat milk seems to be a very appealing candidate for a natural source of human-like oligosaccharides due to its concentration and structure. However, research data on the bioactive oligosaccharides of goat milk is still scarce.

Based on the above, goat oligosaccharides have gained lately much attention as potential nutritional supplements or therapeutic agents. Therefore, they have been used in a number of studies in order to evaluate their health-promoting effects.

#### *6.3.1. Prebiotic and antipathogenic activity*

A healthy gut microbiota, composed primarily of bifidobacteria and lactobacilli, which are bacteria presenting saccharolytic activity, has been linked with multiple health benefits. This can be explained by the interactions of intestinal bacteria with metabolic processes and the endocrine and immune systems of infants and adults. Intestinal colonization with a balanced microbiota is of major importance for the appropriate development of the immune system, and there is an enormous scientific and commercial interest in modifying the microbiota for health promotion [173]. As the gut is sterile at birth, it is an organ sensitive to environmental influences. Furthermore, there is an intensive crosstalk between gut microbes and the intestinal epithelium throughout life [174, 175]. The species present in intestinal microbiota, once established, appear to be difficult to modify. Two strategies have been developed to promote a healthy microbiota: the administration of live bacteria (probiotics); or substances (prebiotics) which pass through the gastrointestinal tract undigested, but constitute substrate for desirable bacteria in the gut. The ability of saccharolytic bacteria to break the bonds present in carbohydrates make them able to use these substances to proliferate in detriment of other bacteria which do not possess enzymes to degrade these products. These bacteria provide additional benefits by producing important nutrients, such as vitamins, amino acids, or short-chain fatty acids, which can then be absorbed by the host. The mechanisms by which the intestinal mucosa perceives and responds to microbes, both pathogenic and commensal, are not completely known yet. Based on the literature and considering the analogy between human and goat milk oligosaccharides we might hypothesise a goat oligosaccharides metabolism and potential functions (**Figure 2**).

short-chain fatty acids such as lactic and propionic acids. However, there was no inhibition

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The ability of oligosaccharides to reduce the pathogen binding to the intestinal mucosa is another feature that should be considered. Certain bacteria and viruses are able to recognize some types of fucosylated and sialylated oligosaccharides (which are present in milk) and adhere to them [178] reducing their adhesion to intestinal cells and consequently the occurrence of infection. Acidic oligosaccharides containing sialic acid are able to block adhesion of *H*. *pylori* [179], *S*. *aureus*, and *Clostridium botulinum* [180]. More recently, Thum et al. [181] investigated catabolism and fermentation of caprine milk oligosaccharides by selected bifidobacteria isolated from four breastfed infants. Results show that dietary consumption of caprine milk oligosaccharides (sialyloligosaccharides) may stimulate the growth and metabolism of intestinal *Bifidobacteria* spp., including *Bifidobacterium bifidum*, typically

Martinez-Ferez et al. [182] suggested that goat milk oligosaccharides may have an anti-inflammatory action. Their research aimed to investigate whether goat's milk oligosaccharides could inhibit the adhesion of monocytes to human umbilical vein endothelial cells. The results of this research indicated that goat's milk oligosaccharides may in fact act as anti-inflammatory agents in the newborn infant, an effect that had already been demonstrated for human milk oligosaccharides and that can be attributed to the structural similarities between goat and human milk

The studies of Lara-Villoslada et al. [183] and Daddaoua et al. [184] have evaluated the effects of oligosaccharides isolated from goat milk in rat models of induced colitis. Lara-Villoslada et al. [183] found that goat milk oligosaccharides are actively involved in the repairing process after a DSS-induced colitis. Moreover, the development of the intestinal flora can be stimulated by oligosaccharides containing N-acetylglucosamine that enhance the growth of *B*. *bifidum* [185]. Daddaoua et al. [184] reported that animals previously treated with goat milk oligosaccharides showed decreased colonic inflammation and fewer necrotic lesions compared to the respective controls. The authors suggested that the observed upregulation of the trefoil factor 3, which is involved in tissue repair, could indicate a possible mechanism of action. Although further research is needed in order to validate this approach, the use of goat milk oligosaccharides as part of a therapeutic strategy against inflammatory bowel

Research data suggests that goat milk may be a very appealing source of human-like oligosaccharides The high amount of oligosaccharides in goat milk, as well as their structural profile, as opposed to other domestic mammals, place goat's milk oligosaccharides as the best source for animal-derived oligosaccharides. However, there is still a lack of data concerning the variation of the oligosaccharides profile of goat milk depending on the season, diet, lacta-

of *S*. *aureus* and *E*. *coli* grown in human feces.

found in the large intestine of breastfed infants.

*6.3.3. Prevention of inflammatory bowel disease (IBD) and colitis*

*6.3.2. Anti-inflammatory activity*

oligosaccharides.

disease seems promising.

tion stage, breed, and number of lactation.

One of the main features of oligosaccharides is that they can only be consumed by very specific bacteria strains that possess the appropriate set of enzymes to cleave their complex structure. This prebiotic effect is associated with improved health outcomes because it allows specific changes, both in the composition and/or in the activity in the gastrointestinal microflora [176]. Considering that oligosaccharides are only partially digested in the small intestine, they can reach the colon intact where they selectively stimulate the development of lactobacilli and bifidobacteria. Oliveira et al. [177] evaluated the prebiotic activities of the natural oligosaccharides recovered from caprine milk whey and reported that the natural oligosaccharides from caprine milk whey favored the development of *Bifidobacterium* spp. and produced

**Figure 2.** Metabolism of goat milk and milk derivates oligosaccharides and potential functions (1—influence on the microbiota composition and/or activity; 2—prevention of pathogens adhesion; 3—direct effects on epithelial cells; 4 systemic effects) (adapted from Kunz et al. [172]).

short-chain fatty acids such as lactic and propionic acids. However, there was no inhibition of *S*. *aureus* and *E*. *coli* grown in human feces.

The ability of oligosaccharides to reduce the pathogen binding to the intestinal mucosa is another feature that should be considered. Certain bacteria and viruses are able to recognize some types of fucosylated and sialylated oligosaccharides (which are present in milk) and adhere to them [178] reducing their adhesion to intestinal cells and consequently the occurrence of infection. Acidic oligosaccharides containing sialic acid are able to block adhesion of *H*. *pylori* [179], *S*. *aureus*, and *Clostridium botulinum* [180]. More recently, Thum et al. [181] investigated catabolism and fermentation of caprine milk oligosaccharides by selected bifidobacteria isolated from four breastfed infants. Results show that dietary consumption of caprine milk oligosaccharides (sialyloligosaccharides) may stimulate the growth and metabolism of intestinal *Bifidobacteria* spp., including *Bifidobacterium bifidum*, typically found in the large intestine of breastfed infants.

#### *6.3.2. Anti-inflammatory activity*

influences. Furthermore, there is an intensive crosstalk between gut microbes and the intestinal epithelium throughout life [174, 175]. The species present in intestinal microbiota, once established, appear to be difficult to modify. Two strategies have been developed to promote a healthy microbiota: the administration of live bacteria (probiotics); or substances (prebiotics) which pass through the gastrointestinal tract undigested, but constitute substrate for desirable bacteria in the gut. The ability of saccharolytic bacteria to break the bonds present in carbohydrates make them able to use these substances to proliferate in detriment of other bacteria which do not possess enzymes to degrade these products. These bacteria provide additional benefits by producing important nutrients, such as vitamins, amino acids, or short-chain fatty acids, which can then be absorbed by the host. The mechanisms by which the intestinal mucosa perceives and responds to microbes, both pathogenic and commensal, are not completely known yet. Based on the literature and considering the analogy between human and goat milk oligosaccharides we might hypothesise a goat oligosaccharides metabo-

One of the main features of oligosaccharides is that they can only be consumed by very specific bacteria strains that possess the appropriate set of enzymes to cleave their complex structure. This prebiotic effect is associated with improved health outcomes because it allows specific changes, both in the composition and/or in the activity in the gastrointestinal microflora [176]. Considering that oligosaccharides are only partially digested in the small intestine, they can reach the colon intact where they selectively stimulate the development of lactobacilli and bifidobacteria. Oliveira et al. [177] evaluated the prebiotic activities of the natural oligosaccharides recovered from caprine milk whey and reported that the natural oligosaccharides from caprine milk whey favored the development of *Bifidobacterium* spp. and produced

**Figure 2.** Metabolism of goat milk and milk derivates oligosaccharides and potential functions (1—influence on the microbiota composition and/or activity; 2—prevention of pathogens adhesion; 3—direct effects on epithelial cells; 4—

lism and potential functions (**Figure 2**).

214 Goat Science

systemic effects) (adapted from Kunz et al. [172]).

Martinez-Ferez et al. [182] suggested that goat milk oligosaccharides may have an anti-inflammatory action. Their research aimed to investigate whether goat's milk oligosaccharides could inhibit the adhesion of monocytes to human umbilical vein endothelial cells. The results of this research indicated that goat's milk oligosaccharides may in fact act as anti-inflammatory agents in the newborn infant, an effect that had already been demonstrated for human milk oligosaccharides and that can be attributed to the structural similarities between goat and human milk oligosaccharides.

#### *6.3.3. Prevention of inflammatory bowel disease (IBD) and colitis*

The studies of Lara-Villoslada et al. [183] and Daddaoua et al. [184] have evaluated the effects of oligosaccharides isolated from goat milk in rat models of induced colitis. Lara-Villoslada et al. [183] found that goat milk oligosaccharides are actively involved in the repairing process after a DSS-induced colitis. Moreover, the development of the intestinal flora can be stimulated by oligosaccharides containing N-acetylglucosamine that enhance the growth of *B*. *bifidum* [185]. Daddaoua et al. [184] reported that animals previously treated with goat milk oligosaccharides showed decreased colonic inflammation and fewer necrotic lesions compared to the respective controls. The authors suggested that the observed upregulation of the trefoil factor 3, which is involved in tissue repair, could indicate a possible mechanism of action. Although further research is needed in order to validate this approach, the use of goat milk oligosaccharides as part of a therapeutic strategy against inflammatory bowel disease seems promising.

Research data suggests that goat milk may be a very appealing source of human-like oligosaccharides The high amount of oligosaccharides in goat milk, as well as their structural profile, as opposed to other domestic mammals, place goat's milk oligosaccharides as the best source for animal-derived oligosaccharides. However, there is still a lack of data concerning the variation of the oligosaccharides profile of goat milk depending on the season, diet, lactation stage, breed, and number of lactation.

The beneficial effects of goat milk oligosaccharides are summarized in **Figure 3**. The increasing interest in healthy diets is stimulating development of new products in the food industry, and many studies have been conducted on fermented milk [138]. Taking into account the health benefits from goat milk, this could be a future trend in the field of probiotic fermented milk products. A lack of information still exists regarding traditional goat cheese and its health properties. However, the incorporation of selected lactic acid bacteria in simple and mixed cultures in goat cheese production is an example of recent innovation in this field. Furthermore, caprine milk whey could be an important source of bioactive compounds for the dietary supplement industry.

bioactive compounds in its constitution make goat milk potentially helpful in the treatment

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Several studies conducted on animal models have shown that goat milk can have beneficial effects on inflammatory bowel disease and disorders characterized by malabsorption. Goat milk, its whey, and fermented goat products may reduce the risk of chronic disorders by anti-inflammatory and anti-oxidative effects. Additionally, goat milk and its derivatives can encourage the selective growth of bacteria that are part of the intestinal microbiota, with potential benefits on the metabolic, endocrine, and immune systems. All these mechanisms suggest that the bioactive compounds present in goat's products might have pleotropic

effects. The main health effects of goat-derived products are summarized in **Figure 4**.

Taking all of this into account, goat's milk and other goat derivatives have the potential to act as health-promoting food and to improve overall therapeutic success in the management of chronic diseases, in conjunction with conventional medical treatment. Goat milk is particularly recommended for infants, the elderly, and convalescing people. Therefore, goat milk and dairy products offer exciting opportunities in the area of functional foods. However, this field of research is only in its infancy, as more and more nutrients with physiological effects are being discovered. More studies and clinical trials are necessary, exploring various new fields of study, going as far as to the molecular level, in order to confirm the beneficial effects of such compounds. This will allow for the identification of important pathways in the cells and tissues of the organism and the discovery of new and accessible biomarkers that are indicative of the health benefits promoted by functional foods and their bioactive compounds.

or even the prevention of certain medical conditions.

**Figure 4.** Schematic representation of the main health effects of goat's products.

**Figure 3.** Main health benefits of oligosaccharides present in goat milk and its derivatives.

## **7. Conclusions and future prospects**

Goat milk and other goat-derived products present unique characteristics and their nutritional value, as well as their potential health effects, have been the object of a fair amount of investigation. The composition of goat milk does not differ remarkably from that of cow milk, while presenting more similarities with human milk, making it more easily tolerated. Moreover, the superior digestibility of goat milk, its fatty acid composition, and the presence of various bioactive compounds in its constitution make goat milk potentially helpful in the treatment or even the prevention of certain medical conditions.

The beneficial effects of goat milk oligosaccharides are summarized in **Figure 3**. The increasing interest in healthy diets is stimulating development of new products in the food industry, and many studies have been conducted on fermented milk [138]. Taking into account the health benefits from goat milk, this could be a future trend in the field of probiotic fermented milk products. A lack of information still exists regarding traditional goat cheese and its health properties. However, the incorporation of selected lactic acid bacteria in simple and mixed cultures in goat cheese production is an example of recent innovation in this field. Furthermore, caprine milk whey could be an important source of bioactive compounds

Goat milk and other goat-derived products present unique characteristics and their nutritional value, as well as their potential health effects, have been the object of a fair amount of investigation. The composition of goat milk does not differ remarkably from that of cow milk, while presenting more similarities with human milk, making it more easily tolerated. Moreover, the superior digestibility of goat milk, its fatty acid composition, and the presence of various

for the dietary supplement industry.

216 Goat Science

**7. Conclusions and future prospects**

**Figure 3.** Main health benefits of oligosaccharides present in goat milk and its derivatives.

Several studies conducted on animal models have shown that goat milk can have beneficial effects on inflammatory bowel disease and disorders characterized by malabsorption. Goat milk, its whey, and fermented goat products may reduce the risk of chronic disorders by anti-inflammatory and anti-oxidative effects. Additionally, goat milk and its derivatives can encourage the selective growth of bacteria that are part of the intestinal microbiota, with potential benefits on the metabolic, endocrine, and immune systems. All these mechanisms suggest that the bioactive compounds present in goat's products might have pleotropic effects. The main health effects of goat-derived products are summarized in **Figure 4**.

Taking all of this into account, goat's milk and other goat derivatives have the potential to act as health-promoting food and to improve overall therapeutic success in the management of chronic diseases, in conjunction with conventional medical treatment. Goat milk is particularly recommended for infants, the elderly, and convalescing people. Therefore, goat milk and dairy products offer exciting opportunities in the area of functional foods. However, this field of research is only in its infancy, as more and more nutrients with physiological effects are being discovered. More studies and clinical trials are necessary, exploring various new fields of study, going as far as to the molecular level, in order to confirm the beneficial effects of such compounds. This will allow for the identification of important pathways in the cells and tissues of the organism and the discovery of new and accessible biomarkers that are indicative of the health benefits promoted by functional foods and their bioactive compounds.

**Figure 4.** Schematic representation of the main health effects of goat's products.
