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Nutraceutical is a term derived from nutrition and pharmaceutical. There are many compounds that improve immune responses and reduce the risk of disease through different mechanisms of action.
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Probiotics are the supplementation of viable microorganisms that offer potential health benefits to the animal. Probiotics are predominately supplemented to improve gastrointestinal health, rumen fermentation, or nutrient utilization.
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Prebiotics are a group of indigestible carbohydrates that function to improve the growth of commensal bacteria. Some fractions (eg, β-glucans and mannanoligosaccharides) have direct immunomodulatory, gram-negative pathogen binding, or hydrophobic mycotoxin absorption capacities.
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Phytonutrients are a group of compounds isolated from plants with potential therapeutic applications given their intrinsic antioxidative, anti-inflammatory, and antimicrobial properties.
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Polyunsaturated fatty acids influence the degree of inflammation. Generally, increasing the supplementation of omega-3 fatty acid sources decreases inflammation, whereas supplementation of omega-6 fatty acids increases inflammation. How much inflammation is needed at any specific physiologic stage is less understood in ruminant species.
Introduction
Public concerns regarding the potential association between zoonotic multidrug-resistant bacterial strains and antibiotic use in food animals has prompted significant regulatory changes to on-farm antimicrobial availability and use.
Producers and veterinarians alike face increasingly limited options to therapeutically treat diseased animals. As a result, microbial and plant-based compounds and their derivatives received increased research and commercial attention in the past few decades. Nutraceuticals, as many of them are known, is a hybrid of nutrition and pharmaceuticals. They consist of natural compounds and/or microbes that offer potentially advantageous effects related to ruminant health and productivity, including improved feed efficiency, milk production, and disease resistance through immune modulation or decreased disease pressure.
Nutraceuticals are a broad group of compounds that can be classified in several ways. Some of the more common classifications are based on the mechanism of action, chemical nature, or the feed source of the compound. In this review, we discuss the general mechanisms of action of common nutraceutical classes that are currently available to be used in ruminants. We classify and discuss each nutraceutical as either a probiotic, prebiotic, phytonutrient (eg, polyphenol, spices/essential oils), or polyunsaturated fatty acid. Finally, nutraceuticals are a rapidly developing field and it is important to note that these compounds lack governmental regulatory oversight by the Food and Drug Administration given their classification as “dietary supplements.” Therefore, product label statements regarding composition, dosage, effectiveness, and quality are not necessarily independently validated or standardized.
Probiotics
Probiotics, also known as direct-fed microbials, can improve health in many animal species. Common probiotic microorganisms currently used commercially include Lactobacillus sp. and other lactic acid-producing bacteria, Bifidobacterium sp., Bacillus sp., and Saccharomyces cerevisiae. Important considerations when supplementing probiotics include the dose (colony-forming units [CFU]), the duration of supplementation, and the age of the animal. A significant portion of the research on probiotic supplementation in ruminants focused on the health benefits to the gastrointestinal tract (GIT), which makes teleologic sense because these microorganisms may directly influence microbial communities and cellular function within the GIT. Most of the health benefits described in Table 1 report reduced incidence or duration of scours. Ancillary benefits of probiotics, both direct and indirect, in other organ systems including the respiratory tract, urogenital tract, and mammary gland have also been investigated, but are only briefly discussed in this review.
Table 1Effects of probiotics and prebiotics on the immune function, health, and performance of calves, dairy cows, and feedlot steers
Effects of probiotics supplementation in daily milk intake of newborn calves on body weight gain, body height, diarrhea occurrence and health condition.
Impact of probiotic administration on the health and fecal microbiota of young calves: a meta-analysis of randomized controlled trials of lactic acid bacteria.
Supplementing neonatal Jersey calves with a blend of probiotic bacteria improves the pathophysiological response to an oral Salmonella enterica challenge.
Jacobs Journal of Veterinary Science and Research.2019; 6: 050
Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecal Escherichia coli.
Changes in the intestinal bacterial community, short-chain fatty acid profile, and intestinal development of preweaned Holstein calves. 1. Effects of prebiotic supplementation depend on site and age.
Effects of dietary supplementation of glutamine and mannan oligosaccharides on plasma endotoxin and acute phase protein concentrations and nutrient digestibility in finishing steers.
Concentrations of prebiotics are not standardized, so comparisons among studies are not recommended. Some prebiotics included a carrier that may or may not influence the outcome.
The dynamics of the GIT vary between individual animals, diets, ages, environment, and management factors. Therefore, there is a significant amount of complexity involved in evaluating and comparing the efficacy of these probiotic strategies on their ability to affect health and performance. Typically, a probiotic must contain live microorganisms (usually bacteria and/or yeast) and produce one or more of the following desirable outcomes
Prevent adherence or colonization of potential pathogens in the GIT
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Produce antimicrobial or bactericidal products against potential pathogens
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Maintain host GIT integrity including improved barrier defenses
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Improve mucosal adaptive immune responses
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Regulate GIT inflammation
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Improve ruminal fermentation and nutrient utilization
The application of probiotics in neonates is more common, which makes sense because the GIT and immune system are both developing rapidly and the risk for GIT disease is greater in the neonate. There is a shift in the microbial ecology in the GIT in early life. The neonatal GIT is colonized by many facultative anaerobic bacteria that are common in the environment, including a lot of the family of Enterobacteriaceae that include many strains of pathogenic Escherichia coli and Salmonella sp. There is a shift to more strict anaerobic bacteria as the animal ages with reduced abundance of Enterobacteriaceae.
Many of the probiotic microorganisms supplemented are either strict anaerobes or facultative anaerobes that commonly increase in abundance as an animal increases in age and are more often lactic acid-producing bacteria. Some of the logic is that speeding up this microbial progression will reduce GIT disease, especially by Enterobacteriaceae, because the GIT environment is less conducive to their colonization.
Probiotics can help maintain a beneficial host relationship and colonize the lumen and outer epithelium of the lower GIT creating competition for space on the mucosal surface as well as for nutrients on the mucosa that allow for bacterial adherence and growth (Fig. 1). The more “beneficial” bacteria present on the mucosa taking up space and nutrients the less that is available for pathogenic bacteria and potentially other enteric disease-causing microorganisms such as rotavirus, coronavirus, Cryptosporidium, and Eimeria. This mechanism is often referred to as competitive exclusion. Furthermore, increased lactic acid concentrations in the lower GIT reduces lumen pH and may help limit establishment of pathogenic Enterobacteriaceae.
Another mechanism of action through which probiotics may influence health and performance of animals is via interaction with the GIT mucosal immune system (see Fig. 1). There are specialized cells in the GIT epithelium known as M cells that constantly sample contents from the GIT and deliver antigens to the lymphocyte-rich Peyer’s patches. Maintenance of the commensal microbial structure of the GIT helps regulate the inflammatory response in the small intestine to prevent an overreaction to the commensal microbiome and potentially other enteric pathogens.
The presence of secretory immunoglobulin A (IgA), antimicrobial peptides, and other regulatory leukocyte responses at the GIT mucosa is an important mechanism that regulates proinflammatory responses, which are essential to maintaining GIT integrity and function. Liang et al. (in press) supplemented Jersey bull calves with 2 strains of lactic acid-producing bacteria and challenged them at 7 days of age with a moderate dose of Salmonella enterica serotype Typhimurium. Calves supplemented with probiotic bacteria had reduced systemic inflammation and less mucosal damage as demonstrated by greater villi height:crypt depth in both the duodenum and ileum compared with the unsupplemented, challenged calves.
Supplementing neonatal Jersey calves with a blend of probiotic bacteria improves the pathophysiological response to an oral Salmonella enterica challenge.
Jacobs Journal of Veterinary Science and Research.2019; 6: 050
Localized proinflammatory responses are considered beneficial in most tissues; however, in the GIT mucosa, an excessive proinflammatory response may compromise the integrity of the GIT barrier and further exacerbate the pathogenesis of the disease.
Most of the mechanisms of action of probiotics discussed are to decrease the colonization of pathogenic microorganisms or directly improve GIT mucosal immune responses. However, supplementing probiotic species that either produce or stimulate the production of more butyrate have the potential to alter GIT mucosal defenses (see Fig. 1). Butyrate is one of the short-chain fatty acids produced by bacteria in the rumen and intestines. Butyrate is a preferred energy source for GIT epithelium that results in the proliferation and differentiation of epithelial cells in the rumen and both the small and large intestines. Butyrate can affect barrier development of the small intestine by increasing tight junction protein expression and exhibiting immunomodulatory effects on enterocytes and mucosal surfaces of the GIT by increasing neutrophil migration.
Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.
Current research suggests that butyrate has anti-inflammatory, antioxidant, and anticancer functions along with promoting epithelial cell proliferation and differentiation.
Supplementing butyrate-producing bacteria as probiotics is a relatively novel concept. Furthermore, a process known as cross-feeding has been recently described in which butyrate-producing bacteria are stimulated to proliferate in the presence of lactic acid originating from lactic acid-producing bacteria. Therefore, some of the benefits observed from supplementing common probiotic strains currently used in ruminants may partially be explained by changes in butyrate production in the GIT.
The use of probiotics in mature ruminants (eg, feedlot cattle or lactating dairy cows) can affect the rumen and lower GIT. Some probiotic microorganisms bypass the reticuloruminal and abomasal compartments and exert beneficial effects in the lower GIT, likely through similar mechanisms of action as discussed above for preweaned calves. Supplementing feedlot cattle with lactic acid-producing bacteria decreased E coli O157:H7 and Salmonella sp. fecal shedding, as well as contamination on carcass hides postharvest.
Supplementing probiotics to feedlot cattle as a preharvest food safety strategy is now a common industry practice. Most of the data currently available regarding probiotic supplementation in dairy cow rations have assessed its effect on performance and milk quality (eg, somatic cell count). Fecal pathogen shedding or manure consistency were not commonly reported variables in these studies. It is conceivable that many of the probiotic species discussed previously in neonates may have some lower GIT benefits in mature dairy cows. In fact, some of the performance benefits such as increased milk production may be partially attributable to improvements in GIT health. Furthermore, supplementing probiotics to mature dairy cows seems to have the greatest health and economic benefits during stressful events, most notably the transition period.
The mechanisms of action of orally delivered probiotics on GIT health are more straightforward than how oral probiotics may improve immunity against infections in nonmucosal tissues (eg, mammary gland). The mucosal immune system is a complex network of mucosal surfaces spanning the gastrointestinal, respiratory, and urogenital tracts. Immune responses generated at one mucosal location can transfer to other mucosal surfaces through trafficking and recirculation of effector and memory leukocytes; however, this likely does not include the mammary gland. The paucity of data and the lack of a clear mechanism of action do not support the notion that oral administration of probiotics improves mammary gland health. Rainard and Foucras
discussed the potential direct effects of either intramammary infusion or topical application of probiotics, either lactic acid-producing bacteria or Bacillus sp., that can inhibit the growth of mastitis causing pathogens in a teat dip as a more promising route of administration to improve mammary gland health. Intramammary infusion of a live lactic acid-producing bacteria culture increased the secretion of proinflammatory cytokines interleukin-8 (IL-8) and IL-1 and attracted neutrophils to the mammary gland.
Administration of a live culture of Lactococcus lactis DPC 3147 into the bovine mammary gland stimulates the local host immune response, particularly IL-1 and IL-8 gene expression.
The authors suggested application of this intramammary infusion for the treatment of mastitis because of the production of a broad-spectrum bacteriocin against gram-positive bacteria and a sustained innate immune response.
Finally, a common probiotic application in ruminants is to supplement probiotics, either bacterial or fungal, to improve rumen function and health. The primary mechanisms of action are to stimulate total rumen bacterial population densities, shift or stabilize the balance of rumen bacterial populations, utilize lactic acid, and reduce the risk for ruminal acidosis, and maintain a low oxygen rumen environment.
Establishment of cellulolytic bacteria and development of fermentative activities in the rumen of gnotobiotically reared lambs receiving the microbial additive Saccharomyces cerevisiae CNCM I1077.
Quantification by real-time PCR of cellulolytic bacteria in the rumen of sheep after supplementation of a forage diet with readily fermentable carbohydrates: effect of a yeast additive.
designed well-controlled experiments to elucidate the mechanisms by which live yeast supplements may increase rumen bacterial population densities. Oxygen utilization by live yeast supplements seems to be an important mechanism improving the growth of rumen bacteria. Silberberg and colleagues
supplemented a live yeast during repeated rumen acidosis challenges and reported improvements in rumen pH, a more stabilized rumen bacteria population, and less systemic inflammation. Another microbial strategy to aid in the prevention of rumen acidosis is a bolus inoculation with lactic acid-utilizing bacteria such as Megasphaera elsdenii. Arik and colleagues
administered a bolus of lactic acid-utilizing bacteria to the rumen of Holstein heifers with M elsdenii for 2 consecutive days during a subacute ruminal acidosis challenge. They observed the M elsdenii-treated heifers had a slowed decrease in rumen pH, decreased concentrations of lactic acid-producing bacteria (Streptococcus bovis), and increased protozoa counts. These studies support the notion that microbial supplementation strategies can improve rumen function and health.
Prebiotics
Prebiotics are indigestible carbohydrates, including many oligosaccharides and fructans, that can improve animal health through a variety of mechanisms. One common mode of action is that they serve as an energy source for commensal or probiotic bacteria in both the rumen and the lower GIT.
Fructooligosaccharide (FOS) and galactooligosaccharides (GOS) increase Bifidobacterium but reduce butyrate producing bacteria with adverse glycemic metabolism in heathy young population.
Synbiotic is the term used when a prebiotic is fed with a probiotic and the effect together is greater than if either is fed alone (see Fig. 1). However, the focus of prebiotics in this review is more on their immunomodulatory effects, ability to bind gram-negative bacterial pathogens, and adsorbing certain mycotoxins.
Prebiotics are commonly found in plants, milk, or the cell wall of fungi (yeast and mushrooms). They are found in natural feedstuffs as well as in various extracts. Food sources for galactooligosaccharides include soybeans and milk, whereas fructooligosaccharides are found in vegetables and plants. Prebiotics isolated from yeast cell walls include mannan-oligosaccharides (MOS) and β-glucans (BGs). The composition, availability, and physical chemistry of a prebiotic in a feedstuff or in an extract influences its ability to improve the health of an animal. For example, a prebiotic extract of yeast cell wall may be very different from another extract of yeast cell wall, even if they are extracted from the same strain of yeast.
Methods of extraction (eg, enzymatic, solvents, temperature, and time) and additional processing techniques (eg, deproteination) can significantly influence the functional properties of an extract. Making comparisons among various prebiotics are difficult in that many extracts are blended with other ingredients, so 1 g of “extract A” is likely not equivalent to 1 g of “extract B.” Therefore, caution should be taken when reviewing the dose of a prebiotic in Table 1 and when making comparisons among published studies involving different extracts.
The in vitro binding of yeast cell wall extracts with MOS showed that MOS binds to the type 1 fimbriae expressed on many gram-negative bacteria such as pathogenic Salmonella sp. and E coli.
These mannose -specific filaments, or type 1 fimbriae, bind to MOS and prevent pathogenic bacteria from binding to the epithelium and colonizing the GIT. Thus, supplementing yeast cell wall extracts with MOS may be a useful prevention strategy for those animals impacted by greater exposure to gram-negative pathogenic bacteria.
Because adhesion of pathogenic bacteria to host mucosal surfaces is generally required for an infection in the GIT, the binding of MOS to these fimbriae decreases potential pathogenic adherence to the host GIT mucosa. The impacts of MOS on specific immune responses are not well characterized. Furthermore, complicating interpretation of data is that MOS extracts are predominately yeast cell wall extracts that also contain various glucan fractions including BGs. Therefore, many of the immunomodulatory effects described in the next paragraph are possible when yeast cell wall extracts are supplemented and likely attributed to the BG fraction of the extract.
β-Glucans are cell wall fractions usually isolated from fungal sources and have potential immunomodulatory effects. The β-1,3-glucans are able to bind to Dectin-1 receptors on monocytes, macrophages, and neutrophils, and, to a lesser extent on dendritic and T-cell surfaces.
Ligation of the Dectin-1 receptor when animals are supplemented a fungal extract can cause a slight activation of various leukocyte responses and is currently considered the mechanism of action for a positive immune response. Oral supplementation of BG fractions or yeast cell wall extracts can increase phagocytosis and oxidative burst capacities of immune cells as well as activate an inflammatory response through a nuclear factor κB-mediated pathway. Oral supplementation of BG also affects systemic immune responses in addition to local GIT immune responses. The mechanism of action of BGs is thought to be mediated through specialized M cells that sample intestinal lumen contents. This increased awareness of the immune system allows for mediated inflammation and an enhanced ability of macrophages, neutrophils, and dendritic cells to identify, engulf, and destroy pathogenic bacteria before they have the opportunity to establish an infection in the host.
As discussed previously, yeast cell wall extracts contain varying levels of both MOS and BG, and are commonly supplemented to ruminants and other livestock for potential immunomodulatory effects, binding of gram-negative bacteria, or adsorbing hydrophobic mycotoxins. The quantity of MOS and BG that bypasses the rumen is not well understood. However, it does seem that an appreciable, biological amount of MOS and BG does influence lower GIT because supplementing yeast cell wall extracts reduced stress-related disease, improved mammary gland health, and increased milk production.
Supplementation strategies of yeast cell wall extracts seem to be most effective during periods of stress or increased pathogen exposure. Another application for yeast cell wall extracts is to alleviate some of the negative effects of hydrophobic mycotoxins such as zearalenone. Jouany and colleagues
reported that commercial yeast cell wall extracts with the greatest MOS and BG content adsorbed zearalenone to the greatest extent but were not effective at adsorbing aflatoxin, a hydrophilic mycotoxin. Therefore, a common mycotoxin strategy is to combine a mineral clay and a yeast cell wall extract to gain a more broad-spectrum mycotoxin adsorption capability.
Phytonutrients
Phenolic compounds represent a family of phytonutrients with potential therapeutic food animal applications given their intrinsic antioxidative and anti-inflammatory properties (Table 2). In nature, plants synthesize polyphenols as both a defense mechanism against exogenous pathogens and for cellular protection against ultraviolet irradiation. Rich sources of phenolic compounds fed to ruminants include a multitude of industrial fruit and vegetable coproducts, such as citrus, pomegranate, green tea, grape, and green vegetable processing residues. Following consumption, the rumen microbiome can significantly degrade polyphenols and decrease host bioavailability. However, a proportion of dietary polyphenols will bypass ruminal degradation and enter the GIT. Following intestinal absorption, phenolic compounds enter the peripheral circulation where they may exert their bioactive effects on inflammation, oxidative status, and immune function (Fig. 2).
Effect of supplementing milk replacer with aromatic oregano (Oreganum onites L.) water on performance, immunity and general health profiles of Holstein calves.
Influence of oregano essential oil (OEO) on prevalence and oocyst shedding dynamics of naturally acquired Eimeria spp. infection in replacement dairy heifers.
Effect of essential oils supplementation on growth performance, nutrient digestibility, health condition of Holstein male calves during pre- and post-weaning periods.
The effect of grape seed and grape marc meal extract on milk performance and the expression of genes of endoplasmic reticulum stress and inflammation in the liver of dairy cows in early lactation.
Effects of a plant product consisting of green tea and curcuma extract on milk production and the expression of hepatic genes involved in endoplasmic stress response and inflammation in dairy cows.
Bioavailability and antioxidant capacity of plant extracts rich in polyphenols, given as a single acute dose, in sheep made highly susceptible to lipoperoxidation.
Lambs infected with Haemonchus contortus GIT parasites
Decreased serum APPs at all dosages (Hpt, LBP, a1AGP), regulate SAA in dose-dependent manner, higher ADG in infected, supplemented lambs vs. infected only lambs; reduced adult worm burden to uninfected levels at 6 g/kg group
Effects of supplementation with dietary green tea polyphenols on parasite resistance and acute phase protein response to Haemonchus contortus infection in lambs.
Published studies on the immune effects of feeding flavonoid metabolites specifically to ruminants were limited predominantly to grape, pomegranate, and green tea derivatives.
Byproducts from wine and fruit-juicing industries include pomace, which consists of residual grape pulp, seeds, skin, and stems. Grape pomace contains high concentrations of flavonoid derivatives and tannins, thus acting as a potential reservoir of dietary antioxidant, anti-inflammatory, and antimicrobial phenolic compounds.
Supplementing grape seed and pomace extracts can reduce mRNA abundancy of fibroblast growth factor 21 (FGF21), a stress hormone associated with hepatic fatty acid oxidation and ketogenesis, in transition dairy cows.
The effect of grape seed and grape marc meal extract on milk performance and the expression of genes of endoplasmic reticulum stress and inflammation in the liver of dairy cows in early lactation.
Grape polyphenols lowered leukocyte mRNA expression of superoxide dismutase, an endogenous free radical scavenger, in postpartum dairy cows. This effect suggests the ability of grape polyphenols to decrease superoxide dismutase expression as a consequence of their endogenous antioxidant capacity.
Pomegranate byproducts (eg, seeds, pulp, and peels) contain a potent source of polyphenols, predominantly flavonoids, phenolic acids, and tannins, as well as stereoisomers of vitamin E. Together, these compounds reduce reactive oxygen species and chelate metal ions to induce potentially beneficial immunomodulatory effects in ruminants.
Dairy calves supplemented with pomegranate extracts had increased in vitro synthesis of the lymphocyte-derived cytokines interferon-γ and IL-4, as well as greater total immunoglobulin G (IgG), in response to ovalbumin vaccination. By improving aspects of both humoral and cell-mediated immunity, calves supplemented with polyphenols may have an improved immune response following vaccination.
Hydrolysable tannins may be able to reduce intraluminal oxidation thereby increasing dietary vitamin E bioavailability, suggesting a potential mechanism for antioxidants to improve health.
Green tea leaf extracts, particularly catechins, represent another rich source of phenolic compounds with antioxidant potential. Tea polyphenols reduced accumulations of reactive oxygen intermediates in bovine mammary epithelial cells following a hydrogen peroxide challenge in vivo.
Effects of supplementation with dietary green tea polyphenols on parasite resistance and acute phase protein response to Haemonchus contortus infection in lambs.
Reduced hepatic metabolic stress, coupled with decreased intrahepatic lipid concentrations and acute-phase protein expression, may indicate improved energy status, ultimately leading to improved ruminant health and performance.
Effects of a plant product consisting of green tea and curcuma extract on milk production and the expression of hepatic genes involved in endoplasmic stress response and inflammation in dairy cows.
Essential oils represent another class of phytonutrients with potential antimicrobial and immunomodulatory capabilities. Essential oils (EOs) provide a plant with its unique color and fragrance. Chemically, EOs are composed of a lipophilic mixture of terpenoids, phenolics, and a variety of low-molecular-weight compounds.
The antibacterial mode of action of volatile oils is likely multifactorial with hypothesized mechanisms including disruption of biochemical pathways associated with cell membranes and passage of low-molecular-weight EO derivatives across inner plasma membranes of both gram-positive and gram-negative bacteria. By interrupting cellular energy metabolism, EOs can partially inhibit bacterial growth and functionality and have demonstrated microbicidal effects against common food-borne pathogens, rumen bacteria, and gastrointestinal parasites (see Fig. 2).
Most of the immunologic effects of EOs were investigated in monogastric species. Receptor-mediated responses upon EO supplementation can result in improved mucosal blood flow, altered cytokine and neuropeptide release, and modified immune cell functionality. Volatile oils undergo significant ruminal biodegradation, likely limiting the immunomodulatory and antibacterial effects.
Of the published studies of EOs performed specifically on ruminants, oregano, garlic, and Capsicum oleoresin oils were shown have potential health and immunomodulatory effects.
Oregano (Origanum onite L) oil and its 2 main phenolic derivatives, carvacrol and thymol, offer a potential potent source of antimicrobial and antioxidant capabilities. Oregano oil increased hematologic variables in dairy calves including hemoglobin, packed cell volume, and mean corpuscular volume.
Dairy calves supplemented with oregano water had increased fecal firmness, reduced Enterobacteriaceae shedding, and increased immunoglobulin concentrations.
Effect of supplementing milk replacer with aromatic oregano (Oreganum onites L.) water on performance, immunity and general health profiles of Holstein calves.
However, adult dairy cattle supplemented with EO products containing either garlic, thyme, or oregano failed to cure experimentally induced Streptococcus uberis mastitis following either topical or intramammary administration.
Influence of oregano essential oil (OEO) on prevalence and oocyst shedding dynamics of naturally acquired Eimeria spp. infection in replacement dairy heifers.
Garlic (Allium sativum) and garlic oils have the capacity to eliminate free radical species and reduce lipid peroxidation in vivo. The effects of garlic oil on immunologic variables in mature ruminants are inconclusive. However, Oh and colleagues
recently described the broad immuno-stimulatory effects of garlic oil following intra-abomasal infusion via an increased neutrophil to lymphocyte ratio as well as increased helper (CD4+) T-cell proliferation.
Capsaicinoids, bioactive compounds sourced from flowering Capsicum plants, demonstrated an ability to modulate the acute-phase response in dairy cows, including in response to an intravenous lipopolysaccharide (LPS) challenge.
By potentially affecting both the innate and adaptive branches of the immune system, capsaicinoid supplementation may be particularly beneficial during vaccination events.
However, more research is needed to validate observations using these EO-based compounds in ruminant species.
Polyunsaturated fatty acids
Dietary fat is more than just calories. The composition of fatty acids in fat sources can influence many cellular functions (Table 3). The fatty acid composition of cellular membranes reflects the fatty acid composition of the diet. The physical chemistry of the various fatty acids differs and increasing the incorporation of polyunsaturated fatty acids (PUFAs) can increase the membrane fluidity. Increasing the fluidity of leukocytes can disrupt the organization of cell surface receptors in the plasma membrane, and ultimately alter cellular function.
Supplementing different ratios of short- and medium-chain fatty acids to long-chain fatty acids in dairy cows: changes in milk fat production and milk fatty acids composition.
Effect of supplementation with n-3 polyunsaturated fatty acids and/or β-glucans on performance, feeding behavior and immune status of Holstein Friesian bull calves during the pre- and post-weaning periods.
Supplementation of essential fatty acids to Holstein calves during late uterine life and first month of life alters hepatic fatty acid profile and gene expression.
Lower n-6 to n-3 decreased plasma IL-6 and haptoglobin concentrations after a moderate intramammary LPS challenge, no effect on neutrophil phagocytosis or oxidative burst, greater DMI and 3.5% FCM in the n-6 to n-3 ratio of 4
Effects of altering the ratio of dietary n-6 to n-3 fatty acids on performance and inflammatory responses to a lipopolysaccharide challenge in lactating Holstein cows.
Effects of dietary supplemental fish oil during the peripartum period on blood metabolites and hepatic fatty acid compositions and total triacylglycerol concentrations of multiparous Holstein cows.
Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: I. Uterine and metabolic responses, reproduction, and lactation.
In addition to influencing membrane fluidity, the fatty acid composition of cellular membranes can alter the biosynthesis of various lipid mediators (Fig. 3). The eicosanoid family are some of the most well-known bioactive lipid mediators and include prostaglandins, leukotrienes, and thromboxanes. The balance of omega-6 to omega-3 PUFA in cellular membranes influences the quantity and biological potency of the eicosanoids produced. Generally, eicosanoids from omega-3 PUFAs have a reduced affinity for cyclooxygenase enzymes. They also produce many eicosanoids that have a lower biological activity than those produced from omega-6 PUFAs. This led to the concept that omega-3 PUFAs have a greater anti-inflammatory capacity than omega-6 PUFAs.
Fig. 3Mechanisms of action of omega-3 long-chain polyunsaturated fatty acids.
Preweaned calves fed milk replacer with either 1% or 2% of the total dry matter (DM) replaced as fish oil, which is rich in omega-3 PUFAs, reduced the proinflammatory response when challenged with a large dose of LPS to mimic sepsis.
In a recent study replacing 2% of the total DM with fish oil fed to preweaned calves did not reduce the serum haptoglobin concentrations or mitogen-induced interferon-γ secretion.
Effect of supplementation with n-3 polyunsaturated fatty acids and/or β-glucans on performance, feeding behavior and immune status of Holstein Friesian bull calves during the pre- and post-weaning periods.
Supplementation of essential fatty acids to Holstein calves during late uterine life and first month of life alters hepatic fatty acid profile and gene expression.
supplemented preweaned calves with either a low or high omega-6 linoleic acid milk replacer (0.46% or 9.0% of the total fatty acids, respectively) and reported that the high linoleic acid treatment had many differentially expressed genes in the liver that should predict a reduced risk of infection. The linoleic fatty acid compositions used in the study of Garcia and colleagues likely reflect milk diets based on milk fat (low linoleic acid) and those in which the primary fat source is based on lard (high linoleic acid). The exact PUFA composition or balance of omega-6 to omega-3 PUFAs in milk solids that improves immune responses and overall health remains to be determined. Finally, although short-chain fatty acids are not PUFAs it is important to emphasize their importance in GIT development as we discussed previously in the section on probiotics. Supplementing short-chain fatty acids such as butyrate can improve GIT development and calf performance.
Furthermore, the effect may be more pronounced in milk replacer diets in which the primary fat source is not milk fat. Milk fat already contains a significant quantity of butyrate; however, the exact concentrations of these short-chain fatty acids to supplement in milk replacer are not known.
Supplementing omega-3 PUFAs and altering the omega-6 to omega-3 PUFA ratio to transition and early lactating cows was investigated as a strategy to improve health and production performance. Feeding whole flaxseed as a source of the omega-3 PUFA, specifically α-linolenic acid, from calving until 105 days in milk (DIM) decreased the serum concentrations of the proinflammatory eicosanoid, prostaglandin E2.
Furthermore, decreasing the omega-6 to omega-3 PUFA ratio using calcium salts of fish oil from 14 to 105 DIM decreased the proinflammatory response following a mild intramammary LPS challenge.
Effects of altering the ratio of dietary n-6 to n-3 fatty acids on performance and inflammatory responses to a lipopolysaccharide challenge in lactating Holstein cows.
In contrast, there was no difference in the proinflammatory response in cows when challenged with 10 times the dose of LPS in the mammary gland at 7 DIM whether they were supplemented with fish oil or not.
Effects of dietary supplemental fish oil during the peripartum period on blood metabolites and hepatic fatty acid compositions and total triacylglycerol concentrations of multiparous Holstein cows.
Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: I. Uterine and metabolic responses, reproduction, and lactation.
supplemented 1.5% of the total DM as safflower oil as a source of omega-6 PUFA from 30 d prepartum to 35 DIM. Observations included increased plasma acute-phase proteins, neutrophil proinflammatory cytokines, neutrophil L-selectin, and neutrophil phagocytic and oxidative burst capacities during the periparturient period. Furthermore, cows were switched to a breeding diet at 35 DIM that contained 1.5% of the total DM as calcium salts of fish oil and fed through 160 DIM. Supplementing cows with the calcium salts of fish oil decreased neutrophil proinflammatory cytokine secretion. These data further support that the balance of omega-6 to omega-3 PUFAs in the diets of both calves and cows can influence various immune responses. However, it remains to be determined at what age, physiologic stage, and conditions more inflammation is desirable and vice versa when less inflammation is preferred.
Nutraceuticals represent a group of compounds that may help fill that void because they exert some health benefits when supplemented to livestock. There remains significant ambiguity regarding nutraceuticals because this field is evolving at a rapid pace without regulatory oversight. In this review, we broadly classify and discuss nutraceuticals as either probiotics, prebiotics, phytonutrients, or PUFAs. These compounds work through various mechanisms of action including stabilizing commensal microbial communities, improving mucosal immune responses and barrier function, binding or adsorbing potential pathogens or toxins, improving antioxidant capacity, direct antimicrobial activity, and increasing or decreasing systemic immune responses.
References
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A review of plant-derived essential oils in ruminant nutrition and production.
Effects of probiotics supplementation in daily milk intake of newborn calves on body weight gain, body height, diarrhea occurrence and health condition.
Impact of probiotic administration on the health and fecal microbiota of young calves: a meta-analysis of randomized controlled trials of lactic acid bacteria.
Supplementing neonatal Jersey calves with a blend of probiotic bacteria improves the pathophysiological response to an oral Salmonella enterica challenge.
Jacobs Journal of Veterinary Science and Research.2019; 6: 050
Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecal Escherichia coli.
Changes in the intestinal bacterial community, short-chain fatty acid profile, and intestinal development of preweaned Holstein calves. 1. Effects of prebiotic supplementation depend on site and age.
Effects of dietary supplementation of glutamine and mannan oligosaccharides on plasma endotoxin and acute phase protein concentrations and nutrient digestibility in finishing steers.
Effect of supplementing milk replacer with aromatic oregano (Oreganum onites L.) water on performance, immunity and general health profiles of Holstein calves.
Influence of oregano essential oil (OEO) on prevalence and oocyst shedding dynamics of naturally acquired Eimeria spp. infection in replacement dairy heifers.
Effect of essential oils supplementation on growth performance, nutrient digestibility, health condition of Holstein male calves during pre- and post-weaning periods.
The effect of grape seed and grape marc meal extract on milk performance and the expression of genes of endoplasmic reticulum stress and inflammation in the liver of dairy cows in early lactation.
Effects of a plant product consisting of green tea and curcuma extract on milk production and the expression of hepatic genes involved in endoplasmic stress response and inflammation in dairy cows.
Bioavailability and antioxidant capacity of plant extracts rich in polyphenols, given as a single acute dose, in sheep made highly susceptible to lipoperoxidation.
Effects of supplementation with dietary green tea polyphenols on parasite resistance and acute phase protein response to Haemonchus contortus infection in lambs.
Effect of supplementation with n-3 polyunsaturated fatty acids and/or β-glucans on performance, feeding behavior and immune status of Holstein Friesian bull calves during the pre- and post-weaning periods.
Supplementation of essential fatty acids to Holstein calves during late uterine life and first month of life alters hepatic fatty acid profile and gene expression.
Effects of altering the ratio of dietary n-6 to n-3 fatty acids on performance and inflammatory responses to a lipopolysaccharide challenge in lactating Holstein cows.
Effects of dietary supplemental fish oil during the peripartum period on blood metabolites and hepatic fatty acid compositions and total triacylglycerol concentrations of multiparous Holstein cows.
Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: I. Uterine and metabolic responses, reproduction, and lactation.
Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.
Administration of a live culture of Lactococcus lactis DPC 3147 into the bovine mammary gland stimulates the local host immune response, particularly IL-1 and IL-8 gene expression.
Establishment of cellulolytic bacteria and development of fermentative activities in the rumen of gnotobiotically reared lambs receiving the microbial additive Saccharomyces cerevisiae CNCM I1077.
Quantification by real-time PCR of cellulolytic bacteria in the rumen of sheep after supplementation of a forage diet with readily fermentable carbohydrates: effect of a yeast additive.
Fructooligosaccharide (FOS) and galactooligosaccharides (GOS) increase Bifidobacterium but reduce butyrate producing bacteria with adverse glycemic metabolism in heathy young population.
Supplementing different ratios of short- and medium-chain fatty acids to long-chain fatty acids in dairy cows: changes in milk fat production and milk fatty acids composition.