LITERATURE REVIEW
Glycobiology, an emerging scientific field, has uncovered the essential role of carbohydrates in immune mechanisms, highlighting their potential to enhance animal health and performance while reducing antibiotic usage Recent pressures on the livestock industry to minimize antibiotics stem from concerns over antibiotic resistance, prompting a shift towards functional carbohydrates in animal diets.
Mannan oligosaccharide (MOS), extracted from the yeast cell wall of Saccharomyces cerevisiae, enhances animal performance and health by preventing pathogen adhesion in the gastrointestinal tract (GIT), modifying GIT microbial populations, and boosting immune functions.
The inclusion of Mannan Oligosaccharides (MOS) in swine diets has led to significant variability in growth performance among pigs While some studies indicate minimal effects on Average Daily Gain (ADG), Average Daily Feed Intake (ADFI), and Gain:Feed ratio (G:F) when MOS is administered to weaned pigs, LeMieux et al (2003) found that nursery pigs receiving diets with 0%, 0.2%, or 0.3% MOS supplementation did not exhibit any growth improvements.
Research on the impact of mannan oligosaccharides (MOS) on pig growth performance has yielded mixed results While Davis et al (2004a) found no significant effect of MOS on nursery pigs, other studies, such as those by Dvorak and Jacques (1998) and Kim et al (2000), reported enhancements in growth performance Notably, Rozeboom et al (2005) examined the effects of MOS on two large-scale commercial farms and a university research farm, revealing that MOS contributed to growth improvements on the commercial farms.
Pigs on Farm C demonstrated improved average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) A recent study analyzing the performance of nursery pigs across seven trials indicated that incorporating mannan oligosaccharides (MOS) into the diets of weaned piglets significantly enhanced their ADFI and ADG (Corrigan et al.).
A meta-analysis by Miguel et al (2004) indicates that the growth performance responses to Mannan-oligosaccharide (MOS) supplementation in pigs can vary significantly, particularly depending on the pigs' growth rates Specifically, it was found that pigs exhibiting high growth rates of over 180 g/d showed little to no response to MOS during the initial 1 to 2 weeks post-weaning.
Mannan oligosaccharide (MOS) has the potential to replace pharmacological levels of trace minerals and serve as an alternative to antibiotics in nursery diets Research by LeMieux et al (2003) demonstrated that a 0.2% MOS supplementation during phase 2 enhanced the growth performance of pigs when excess zinc was excluded from the diet However, when dietary zinc was included at 3000 ppm, there was no significant difference in growth performance between pigs fed MOS and those on a control diet Conversely, Davis et al (2004a) found that MOS supplementation improved growth responses when dietary zinc levels were restricted to 200 or 500 ppm, suggesting that the commonly added zinc levels in nursery pig diets can be reduced in MOS-supplemented formulations.
Feeding pigs with Mannan Oligosaccharides (MOS) can mitigate the negative environmental effects of excess zinc due to decreased zinc excretion Research by Davis et al (2002a) demonstrated that growth benefits in pigs were observed when dietary copper levels were restricted Additionally, MOS presents a viable alternative to antibiotics in specific situations A study by Rozeboom et al (2005) assessed the impact of MOS on medical treatments, removal rates, and mortality in nursery pigs on commercial and university farms, concluding that MOS may serve as a substitute for tylosin and sulfamethazine as growth promoters in nursery diets.
Research indicates that mannan oligosaccharides (MOS) significantly enhance the growth performance of young pigs, both in university research settings and commercial farms The positive impact of MOS is particularly evident in diets with reduced copper and zinc levels, highlighting its potential as an environmentally friendly alternative Further studies are needed to explore MOS as a growth-promoting substitute for antibiotics in pig nutrition.
Research on the impact of dietary Mannan-oligosaccharides (MOS) on poultry growth performance has shown mixed results While some studies, such as Geier et al (2009), found that a 0.5% MOS supplementation did not enhance broiler chicken performance compared to a control group, others, like Fritts and Waldroup (2003), reported no significant difference in turkey poults fed 0.05 or 0.1% MOS versus a negative control Conversely, Zdunczyk et al (2005) identified positive growth effects in turkeys when MOS was included in their diets, highlighting the varying responses to MOS supplementation in poultry nutrition.
Research indicates that turkeys fed diets with medium and high levels of Mannan-Oligosaccharides (MOS) achieved greater body weight (BW) at 16 weeks compared to those on a control diet Studies, including those by Sims et al (2004), confirmed that turkeys receiving 0.05% or 0.1% MOS had heavier BW than control groups A meta-analysis by Hooge (2004a,b) demonstrated that diets enriched with MOS significantly enhanced final BW in both broiler chickens and turkeys, showing comparable results to diets containing sub-therapeutic levels of antibiotics Therefore, the evidence suggests that MOS may serve as an effective growth promoter for poultry.
Research on the growth-enhancing effects of Mannan Oligosaccharides (MOS) has been conducted across various animal species, including cattle, rabbits, and fish Heinrichs et al (2003) found that calves fed MOS exhibited increased Average Daily Feed Intake (ADFI) compared to those receiving antibiotics, although no significant growth difference was observed over the 5-week study period Similarly, Terre et al (2007) reported positive outcomes in calves consuming 4 g of MOS daily In rabbits, feed efficiency improved when MOS was included at levels between 0.05% and 0.2% compared to controls Additionally, a study on rainbow trout indicated that MOS not only enhanced feed efficiency but also improved overall growth performance (Staykov et al., 2007).
Changes in Microbial Population through Agglutination of Pathogens
Mannan oligosaccharide (MOS), extracted from the cell wall of Saccharomyces cerevisiae, is known to enhance gut health by inhibiting pathogen adhesion to the intestinal epithelial surface (Kocher and Tucker, 2005) The mannan component in MOS provides competitive binding sites for specific bacteria, effectively preventing the attachment of harmful pathogens (Oyofo et al., 1989a, b) This mechanism of action is fundamental to the protective benefits of MOS against pathogenic bacteria.
Type I fimbriae adhere to the intestinal wall of animals, allowing harmful bacteria to accompany digesta into the large intestine, where they are eventually excreted in feces A survey revealed that around 70% of 77 Escherichia coli strains and 53% of 30 Salmonella species with Type 1 fimbriae showed sensitivity to mannan (Finuance et al.).
Research by Spring et al (2000) confirmed that mannan oligosaccharides (MOS) inhibit pathogen colonization by screening various bacterial strains for their ability to agglutinate with MOS in yeast cell preparations They found that five out of seven Escherichia coli strains and seven out of ten Salmonella strains, including Salmonella typhimurium and Salmonella enteriditis, were agglutinated by MOS Additionally, Miguel et al (2006) demonstrated that MOS altered the microbial populations in the gastrointestinal tract of young pigs, leading to a reduction in pathogenic bacteria This shift in gut microflora may help prevent diarrhea, promoting overall gut health.
Fecal Score Consistency and Diarrhea
MANNAN OLIGOSACCHARIDE REGULATES CYTOKINE
ALVEOLAR MACROPHAGES IN NURSERY PIGS
Mannan oligosaccharide (MOS) and yeast cell wall derivatives enhance nursery pig growth, yet their mechanisms remain unclear This study tested the hypothesis that MOS reduces systemic inflammation in pigs by assessing cytokine production from alveolar macrophages (AMΦ) and serum cytokine levels Pigs were fed diets with 0.2% or 0.4% MOS for 2 or 4 weeks post-weaning, compared to control diets without MOS Alveolar macrophages were isolated and stimulated in vitro with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C).
Lipopolysaccharide-stimulated AM from pigs fed with mannan oligosaccharide (MOS) produced significantly lower levels of tumor necrosis factor-α (TNF-α) (P < 0.01) and higher levels of IL-10 (P = 0.051) compared to AM from control-fed pigs However, mannan oligosaccharide did not influence cytokine production when AM were stimulated with Poly I:C, and there were no significant differences in serum levels of TNF-α.
and IL-10, although these levels changed over time These results establish that feeding MOS to pigs for 2 wk reduces TNF- and increases IL-10 following in vitro treatment of
A study demonstrated that mannan oligosaccharide (MOS) influences the cytokine production of alveolar macrophages (AMΦ) in response to lipopolysaccharide (LPS) Specifically, MOS significantly suppressed LPS-induced TNF-α secretion (P < 0.001) while simultaneously enhancing LPS-induced IL-10 secretion (P < 0.05).
A study demonstrated that a mannan-rich fraction (MRF) effectively suppresses TNF-α production in AMΦ cells stimulated by LPS (P < 0.05) or Poly I:C (P < 0.001), indicating that both MRF and MOS inhibit LPS-induced TNF-α production.
To investigate the interaction between MOS and LPS receptors, AM were treated with Polymyxin B, a known inhibitor of LPS-activated toll-like receptor 4 The results showed that while Polymyxin B effectively blocked the LPS-induced production of TNF- by AM, it did not alter the overall functionality of these immune cells.
Mannan oligosaccharides (MOS) effectively regulate cytokine production without the presence of lipopolysaccharides (LPS), as demonstrated by their ability to modulate the constitutive production of TNF-α in vitro These findings highlight MOS as a powerful immunomodulator, capable of reducing TNF-α levels while enhancing IL-10 synthesis following ex vivo challenges with bacterial endotoxin in porcine alveolar macrophages (AMΦ).
Mannan oligosaccharide (MOS), derived from the cell wall of yeast Saccharomyces cerevisiae, is a growth promoter in young pigs and poultry (Hooge, 2004a,b; Miguel et al.,
Mannan oligosaccharides (MOS) enhance animal performance by inhibiting the attachment of pathogens with Type I fimbriae to the intestinal wall, leading to healthier guts as harmful bacteria are excreted Research indicates that MOS positively influences both innate and humoral immunity, increasing phagocyte activity in a dose-dependent manner and reducing hypersensitivity reactions in pullets Additionally, feeding MOS boosts immunoglobulin levels in plasma, bile, and colostrum While these findings demonstrate the impact of MOS on immune function, further investigation is needed to clarify its specific effects, particularly regarding cytokine secretion under varying conditions.
Cytokines produced by innate immune cells, such as macrophages, play a crucial role in regulating immune functions and influencing various metabolic processes A balanced interplay between pro-inflammatory cytokines (like IL-1, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokines (such as IL-10) is essential for optimal growth responses and the effective operation of the immune system in the face of immunological challenges.
This study aimed to investigate the impact of mannan oligosaccharides (MOS) on cytokine production by alveolar macrophages (AMΦ) in response to bacterial and viral infection models Additionally, it evaluated how varying dietary levels of MOS influence serum cytokine levels and the growth performance of nursery pigs.
The study received approval from the University of Illinois Institutional Animal Care and Use Committee and involved 160 barrows and gilts, approximately 20 days old and weighing 6.5 ± 1.1 kg BW, which were blocked by body weight and randomly assigned to five treatments in a randomized complete block design Each pen maintained an equal distribution of males and females, with ancestry balanced across treatments Upon entering the nursery facility after weaning, the pigs were fed five experimental diets: a control diet with 0% mannan oligosaccharide (MOS) supplementation, and diets with 0.2% MOS for either 14 or 28 days post-weaning, and 0.4% MOS for the same durations Mannan oligosaccharide was supplied by Alltech, Inc (Nicholasville, KY), and each treatment included eight replicate pens with four pigs per pen.
Pigs were housed in a climate-controlled nursery, with continuous access to feed and water Each pen, measuring 1.32 x 1.32 meters and featuring a metal slatted floor and a nipple waterer, provided an optimal environment for growth The pigs were fed a basal diet formulated to meet or exceed their essential nutritional requirements during the nursery period, according to NRC guidelines (1998).
A pig‟s BW was recorded at weaning (d 0) and on d 7, 14, 21, and 28 PW, and feed disappearance was measured each wk, for calculation of ADG, ADFI, and G:F for each pen
At 14 days post-weaning (PW), one pig from each of six pens per treatment group was slaughtered to collect alveolar macrophages (AM) These macrophages were then stimulated in vitro using lipopolysaccharide (LPS) and Poly I:C, and the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) in the supernatants were subsequently measured.
Blood samples were collected from one pig per replicate pen at days 7, 14, 21, and 28 of the experiment, totaling eight pigs per treatment Each sample consisted of ten milliliters of blood drawn into glass tubes without anticoagulants, allowing the blood to clot at room temperature The samples were stored overnight at 4°C before serum was harvested through centrifugation The serum was then frozen at -80°C for subsequent analysis of TNF-α and IL-10 using ELISA kits.
Collection and Isolation of AM
Alveolar macrophages were collected from 5 to 6-wk-old donor pigs not fed experimental diets or from pigs fed diets with different levels of MOS for 2 wk PW Pigs
A total of 42 pigs were anesthetized using a 1-mL intramuscular injection of a combination of telazol, ketamine, and xylazine in a 2:1:1 ratio, corresponding to 100 mg telazol, 50 mg ketamine, and 50 mg xylazine per 23.3 kg body weight Following anesthesia, the pigs were euthanized via intracardiac injection of sodium pentobarbital at a dosage of 78 mg per kilogram of body weight.
Alveolar macrophages were isolated through pulmonary lavage using 150 mL of PBS without Ca and Mg The lavage fluid was filtered with sterile gauze and centrifuged at 400 x g for 15 minutes at room temperature Following centrifugation, the lung lavage cells were washed with Hank's balanced salt solution and re-suspended in 5 mL of Roswell Park Memorial Institute 1640 culture medium, supplemented with 10% heat-inactivated fetal bovine serum, penicillin (100 IU/mL), and streptomycin (100 µg/mL) Cell viability was assessed using Trypan Blue dye exclusion, yielding a viability rate exceeding 97%, with cell concentration adjusted to 1 x 10^6 cells/mL.
“alveolar macrophages” throughout this paper because the majority (93 to 97.5%) of bronchoalveolar lavage fluid cells is macrophages (Shibata et al., 1997; Dickie et al., 2009)
Culture and Stimulation of AM