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Nutrition and immunity: Odd couple underlying animal health

Barry Bradford and Kai Yuan Published on 22 August 2014

While doing some digging for an undergraduate nutrition course recently, I came across an interesting controversy from the early years of nutrition science.

It seems that Louis Pasteur, the renowned scientist who was responsible for identifying microbes as the causative agents of many diseases, dismissed suggestions that some diseases could be caused by nutritional deficiencies.



Having made such an important discovery, Pasteur was resistant to other explanations, and his influence probably delayed the discoveries that terrible diseases like beriberi and pellagra were actually caused by nutritional deficiencies.

Thankfully, veterinarians and nutritionists today generally embrace the importance of both nutrition and immunity in supporting animal health (though it remains tempting to point the finger elsewhere when problems occur).

However, in our efforts to support the health and productivity of transition cows, sometimes it feels as if we are back in the early days of nutrition and microbiology, grasping for answers to problems that can come and go in waves without any obvious explanation.

The transition cow is an incredibly complex animal, with a host of changes occurring simultaneously, some of which are at odds with one another.

For most readers, the focus on transition cows needs no explanation. The two-week to three-week period after calving typically accounts for 25 to 50 percent of health problems on the farm, and high cull rates in early lactation are a costly problem for many dairies.


What can we do about this? It is true that high rates of transition disorders are often difficult to blame on a single factor. However, this does not mean that we cannot identify important risk factors to eliminate or do a better job of meeting the cow’s biological needs.

Nutrition is clearly a key piece of this puzzle. Nutrients influence health in many different ways, which can be grouped into the following three categories:

  • Gut health – A structurally intact, properly functioning gastrointestinal tract has always been a focus of ruminant nutritionists. However, even in ruminant nutrition we did not fully grasp the importance of the “helpful” microbes in the gastrointestinal tract until the last several years.

    Gut microbes are now thought to contribute to an almost unbelievable array of processes in animals, from maturation of the immune system to influencing food preferences.

  • Metabolic health – Maintenance of nutrient homeostasis is critical to sustaining function of the nervous system, muscles and essentially all organ systems in the body. This is particularly apparent in the transition dairy cow, where extreme shifts in nutrient movement between organs can challenge the ability of the cow to adapt.
  • I mmune function – Traditionally, animal nutritionists have not spent much time thinking about the immune system; that was perhaps considered to be the job of veterinarians dealing with infected animals.

    However, we now understand that the immune system is constantly responding to a variety of stimuli, and that these responses impact animals in more subtle ways than just preventing (or failing to prevent) overt disease. Immune function can be influenced by absorbed nutrients, metabolites and through signals released by sentinel cells lining the gut.

These three components of health are not mutually exclusive. For example, a poorly formulated diet may provide inadequate fiber, leading to acidosis, negatively impacting ruminal microbes and perhaps even breaching the rumen wall barrier.

Ruminal acidosis is associated with the appearance of endotoxin in the bloodstream, which causes inflammation in the liver and alters metabolic function. Acidosis often disrupts feeding behavior, which can lead to ketosis, at least in transition dairy cows.


Ketone bodies, in turn, impair the ability of immune cells to kill invading pathogens. Therefore, a single nutritional problem can negatively influence all three aspects of health.

Supporting immune function through nutrition
The immune system is typically separated into two arms: the adaptive and innate immune systems. The adaptive immune system includes cells that produce antibodies and “remember” pathogens to allow for an aggressive response on subsequent exposure.

The innate immune system, in contrast, is far less specific in its attack strategies, allowing it to respond immediately when bacterial, fungal or viral molecules are recognized.

Dairymen have been accustomed to priming the adaptive immune system for many years through vaccination protocols, but the rapid-response innate arm of the immune system has received little attention until recently.

We now recognize a number of nutrients that can support a potent innate immune response to pathogens, which can help to prevent a small infection from developing into systemic illness. Here are a few interesting examples:

  • Dietary antioxidants are important for protecting against the accumulation of reactive oxygen species, which are particularly harmful for immune cells. Oxidative status can decline in stress-inducing situations such as the transition to lactation and high temperature or humidity environments.

    In such situations, adequate selenium and relatively high vitamin E supplementation rates have improved health outcomes in many studies. However, it is important to remember that if some supplementation is good, more is not always better; vitamin E status of dry cows can be assessed before supplementation of more than 2,000 IU per day is attempted.

  • Though adequate dietary fiber is critical for cow health, the balancing act is to ensure energy supply is not excessively constrained. Insufficient energy intake in early lactation is the primary factor driving metabolic problems such as ketosis and fatty liver.

    Likewise, negative energy balance is associated with poor immune function, likely at least partially because metabolites, like ketone bodies that are elevated in this state, impair the function of innate immune cells.

  • Subclinical hypocalcemia occurs in most transition cows, despite the fact that relatively few cows today suffer from milk fever. This problem is tied to decreased immune function because immune cells from cows experiencing hypocalcemia showed weak responses to stimulation in a lab experiment.

    Such findings may provide a physiological basis for the reported associations between hypocalcemia, mastitis and metritis, and highlight a reason to evaluate calcium status even in herds where milk fever is rare.

  • Choline aids in prevention and resolution of fatty liver in transition cows. Recent evidence also suggests that it can decrease the incidence of mastitis during this period, probably by improving immune function as a secondary response to improved metabolic function.

Bidirectional links
As the choline and calcium examples highlight, metabolic disorders put immune function at risk. Likewise, the inflammation resulting from an infection can suppress feed intake and milk yield and promote metabolic disorders.

On-farm studies have demonstrated clear links between infectious and metabolic disorders. In one study, transition cows with signs of inflammation were at an eightfold greater risk for experiencing one or more transition disorders, had lower plasma calcium concentrations, took longer to re-breed and produced less milk in the first month of lactation.

Other studies have shown that elevated blood markers of negative energy balance (BHBA and NEFA) are associated with twofold to fourfold greater risk of suffering from a clinical infection later.

In fact, decreased feed intake was observed before calving in cows that ended up with subclinical ketosis or metritis after calving, suggesting that behavioral changes and nutrient imbalances can precede key transition problems by days, if not weeks.

These effects can all too easily lead to a downward spiral where declining metabolic function and immune status feed off of each other, leading to complex diseases and cows that don’t stay in the herd to complete their lactation.

The links between nutrition and immunity highlight the importance of viewing health problems in transition cows from a holistic perspective. Let’s remember the lesson of Dr. Pasteur and keep many contributing factors in mind when solving problems on our dairies. PD

Kai Yuan, MS, is completing his Ph.D. at Kansas State University.

References omitted due to space but are available upon request. Click here to email an editor.

barry bradford

Barry Bradford
Associate Professor
Department of Animal Sciences
Kansas State University