Feeding for immunity:
Why the source of trace mineral matters

Required to develop and support a fully functioning immune system, trace minerals support enzyme production. Their availability is linked to functions such as cellular metabolism, tissues integrity, reproduction, growth, microbial modulation, feed intake and other vital functions. But it is important to highlight, not all sources of trace mineral are the same. The structure of trace mineral source influences how much of the metal will be available for absorption and subsequent body utilization.

Davi Brito De Araujo
Global Program Manager Trace Minerals
Trouw Nutrition

As essential nutrients required for animal health and performance, trace minerals are a good example of how small dietary components can have a big impact.

Selko (the Feed Additive brand of Trouw Nutrition) research has pointed out that supplementing diets of weaned pigs, broilers, ruminants and dairy cows with a more stable and less reactive – and consequently more bioavailable – trace mineral source generated improved antioxidant and immune response. Compared to animals receiving sulfate-based trace minerals in their diets, animals receiving hydroxy trace minerals (IntelliBond) had reduced production of oxidative stress markers. Researchers also observed that diets containing hydroxy trace minerals supported animals’ intestinal integrity and were related to a reduced presence of pathogenic bacteria.

ENDURING CHALLENGES AND LIMITED INTERVENTIONS
Today’s livestock producers are striving to raise livestock efficiently and effectively while curbing antibiotic use and reducing levels of antimicrobial feed additives like zinc and copper. Consumers also are paying attention to animal welfare and environmentally responsible livestock production. Tools and practices producers can use to address these concerns include selecting for the best genetics, using good farm management practices, feeding good quality feed and supporting animal health from a preventative rather than curative position. These steps can also support animals’ health and productivity.

DIET DESIGN
Diet design can proactively support animal health and welfare, and includes choosing ingredients that meet animals’ needs for energy, amino acids, vitamins and trace minerals. During periods of increased stress (e.g. weaning, lactation) producers can use synergistic feeding strategies to provide added nutritional support.

IMMUNE SYSTEM FUNCTIONING
Proper nutrition helps support functioning of the immune system (immunocompetence). When pathogens attack, the immune system has a range of response systems. The innate system the animal is born with protects against various antigens. The passive system is a temporary immune response inherited or acquired through pathways like colostrum intake. The adaptative system responds when the innate response is insufficient, and the immune system is overwhelmed, triggering thus a highly specific inflammatory response. In common pathogens like E. coli or PRRS, once the pathogen enters the body components within the immune system, like macrophages, recognize the intruder. These components trigger a signaling pathway to spark an immune response such as the production of pro-inflammatory cytokines. Other acute responses to pathogens include fever, reduced feed intake and a drop in growth. Cytokine production during an immune reaction influences the animal’s metabolic processes because it shunts nutrients to the immune system. For example, during an increased immune response to pathogens in broiler chicks, 9% of the animal’s total lysine may be diverted to the immune response rather than the typical 0.5-2% used.

Figure 1. When the immune system recognizes the presence of pathogenic bacteria it triggers an immune response . Adapted from Johnson, 2012

Along with pathogen-based immune triggers, animals facing stressors like high temperatures, or feed and space restrictions, generate reactive oxygen species or free radicals which cause cellular damage and tissue injury. Extreme stress reactions also can hamper immune functions, animal growth and fertility. Diets that do not provide the needed nutrients can inhibit full immune function, leaving animals more exposed to disease and pathogens.

TRACE MINERAL FUNCTION AND INTERACTIONS
Required to develop and support a fully functioning immune system, trace minerals support enzyme production. Their availability is linked to functions such as cellular metabolism, tissues integrity, reproduction, growth, microbial modulation, feed intake and other vital functions.

But it is important to highlight, not all sources of trace mineral are the same. The structure of trace mineral source influences how much of the metal will be available for absorption and subsequent body utilization. Trace metals can only be used after they’re absorbed in the intestinal tract and enter the blood stream.

Trace mineral sources differ based on bond strength and concentration. Sulfate trace minerals bind metal ions using a relatively weak ionic bond. Easily broken bonds allow the metal to separate when it contacts moisture, allowing it to react with other feed elements. Whether moisture is encountered in humid conditions or during processing, it can increase the possibility that the trace mineral is not available to the animal in the gastrointestinal tract (GIT). Trace minerals dissolving outside of the GIT, aren’t available to the animal. Additionally, reactions can interfere with other functions – like reducing fiber and dry matter digestion in the rumen. And minerals not absorbed will be excreted into the environment.

Organic trace minerals use a stronger covalent bond. However, molecule size of ligand – generally amino acids and peptides – reduces total concentration of the trace mineral element in the molecule, increasing price of unit of metal per kg of product. Hydroxychloride-based trace minerals also have a stronger covalent bond, but once ligands are smaller in size, such as hydrogen, chloride and oxygen, allows greater metal potency per kg of product.

Figure 2. Trace mineral sources have different chemical qualities altering metal availability, reactivity, and concentration.

TRACE MINERALS AND WEANING SUPPORT
Several studies have found that zinc can alleviate or help mitigate gut inflammation and resulting problems during stressful times, such as vaccination, shipping and weaning. Additionally, legislation in many regions mean that therapeutic levels of zinc are not options for treating conditions like diarrhea. A study done at Oklahoma State University explored how different levels and sources of the trace mineral influenced GIT dysbiosis in weaning pigs.

Figure 3. Post-disease challenge, swine receiving a diet supplemented with hydroxychloride-based trace minerals saw a milder response to external stress.

The two trial diets included a sulfate-based or hydroxychloride-based zinc, copper and manganese diet. Pigs also faced an LPS challenge on days 29, 31, 33 and 35. In the hours following the challenge, there was an increase found in the production of TNF inflammatory cytokines. However, three-hours post challenge, swine receiving the hydroxychloride diet were better able to regulate the immune response.

Pigs in the challenge also were tracked for growth performance. At the end of the trial, average daily feed intake was higher for pigs on the hydroxychloride diet and average daily gain was 30g/day higher compared to pigs receiving sulfate-based diets.

Figure 4. Looking at growth performance metrics, animals on the hydroxychloride diet outperformed those on the sulfate diet. Control group animals did not face the disease challenge.

A swine study, done in Iowa looked at immune competence in gilts on diets supplemented with either sulfate or hydroxychloride trace minerals. Diets included 120mg/kg zinc, 15mg/kg copper and 50mg/kg magnesium. Almost 20,000 gilts were orally acclimated to PEDV and researchers tracked how long it took their immune systems to recognize the disease. Gilts receiving the hydroxychloride took longer to present PEDV in their saliva and they demonstrated an immune system more efficient at eliminating the viral challenge.

Studies performed in 2020 at The Autonomous University of Barcelona and North Carolina State University looked at antioxidant activity in weaned pigs during a period of environmental stress. Pigs received diets with 110mg/kg zinc and15mg/kg copper. Pigs on the hydroxy diet generated higher levels of antioxidant enzymes.

Figure 5. Gilts on a Hydroxychloride trace mineral diet were better able to fight off an immune challenge from PEDV compared to animals on a sulfate diet.

A study at the University of Kentucky looked at the difference in response to multiple parities based on the type and amount of copper in the diet. Researchers found that animals on the hydroxychloride diets were able to produce a greater antioxidant response.

The response to mineral type was observed in other species. A study done in 2019 looked at antioxidant activity in 1,080 broilers raised on diets that included 80mg/kg zinc and 15mg/kg copper from either a sulfate or hydroxychloride source. Broilers were tracked for their production of the oxidative stress markers methyl malonic acid and uric acid. Birds on the hydroxychloride diet generated lower levels of both acids.

ASSESSING RUMINANT IMMUNE FUNCTION
Dietary trace mineral source influence also was examined in dairy cows. A recent study done at Cornell University compared the inclusion of three types of trace mineral top-dress blends in cow feed – sulfate, combined sulfate and organic, or hydroxychloride. Cows were tracked from the prepartum period through 84 days in milk. Throughout the trial period, cows on the hydroxychloride diet produced lower levels of TBARS, indicating that animals faced less oxidative stress. In the postpartum period, only the cows receiving the hydroxychloride minerals showed a return to healthy haptoglobin production. This indicates a reduction in stress as healthy cows produce little. Cows in this group were also the first to reach peak milk production and tended to generate more milk (about 1.1 kg/d) throughout the production cycle.

Figure 6. Pigs were better able to manage environmental stress when supported by a diet using hydroxychloride trace minerals in place of sulfate trace minerals.

A study done at Iowa State University in 2020 tracked the influence of zinc trace mineral source on inflammation biomarker production. The project also looked at intestinal integrity using Cr-EDTA as a marker – the more Cr-EDTA that moved out of the intestinal tract into the bloodstream, the more of a “leak” or intestinal damage that had occurred. In this 2 × 2 factorial trial, dairy cows resigned to one of four diets – a non-restricted feed with sulfate-based trace mineral zinc, a non-restricted feed with hydroxychloride trace mineral zinc and two restricted diets, one with either of the two trace mineral sources. Cows were acclimated to the type of diet for an initial period then changed to ad libitum or restricted feed amounts and checked for biomarkers and gut integrity.

Changes to gut morphology found that villus height in the duodenum, jejunum and ileum remained relatively consistent for cows on the hydroxychloride restricted diet and the non-restricted control diet. But cows on the restricted sulfate diet saw a decline in villus height in the ileum. Goblet cells are important for mucus production in the gut. Cows receiving feed restricted diets also reduced goblet cell area compared to ad-libitum treated cows. But also in feed restricted cows, hydroxychloride supplementation supported to increase these cells area in the duodenum when compared to sulfate-fed cows.

Figure 7. Sows receiving hydroxychloride trace minerals were able to generate a greater antioxidant response in stress periods.

Regarding inflammation markers, cows on the restricted diets demonstrated higher levels of lipopolysaccharide binding protein (LBP) serum amyloid A (SAA) and haptoglobin, which was expected. Looking at results for restricted-feeding cows on the hydroxychloride diet, researchers saw improved results compared to cows on the sulfate diet. Both SAA and haptoglobin levels responded to feed restriction but it was much lower for the cows under hydroxychloride diets, indicating that these cows have mitigated more or exacerbated less the inflammation process. LBP levels were higher, for cows getting hydroxy zinc. This observation indicates that the cows’ immune systems were recognizing and responding faster to the increased presence of LPS or pathogenic bacteria.

Although feed-restricted cows saw declines in neutrophil function, when results for cows on the two restricted diets were compared those receiving hydroxychloride zinc had better performance. Cows receiving hydroxychloride-based zinc also had a 67% decrease in the abundance of treponema – a pathogen related to foot rot.

Combined results indicate that while the feed restriction impeded gut integrity, using hydroxychloride minerals compared to sulfate-based minerals helped ameliorate some effects and support intestinal barrier integrity. The difference in trace mineral source could be prompting these differences by being more available along the GIT and providing more of the metal for the cow to use. More metal availability supports better enterocyte health, which helps lower bacterial infiltration and reduce the occurrence of inflammation.

Figure 8. Trace mineral source in dairy cows can reduce stress markers caused by oxidative stress and shorten the time to reach peak milk production.
Figure 10. Trace mineral source can improve gut integrity, immune system function and help reduce indicators of oxidative stress.

CONSIDER THE SOURCE
Beyond immunity, trace minerals influence microbial modulation, gene expression and can contribute to feed palatability. Less reactive, more bioavailable trace minerals may also lower excretion of metal nutrients into the environment.

References available upon request.