Alternative strategies to reduce the use of antibiotics in animal production, using innate host defense mechanisms

Reducing the use of antibiotics in livestock is vital for the control of infectious diseases in humans and animals. Dr Albert van Dijk, author of a recent review published in Veterinary Research, takes us through new approaches that exploit the innate power of the immune system to provide alternatives to antibiotics in animal production.

In livestock, particularly in pig, cattle and poultry farms, closely related antibiotics are used to prevent disease outbreaks and at amounts that surpass the use of antibiotics in humans.

Few people realize that the many antibiotics originate from only a few basic structures, such as penicillins and cephalosporins. Over decades we have grown accustomed to the luxury that our general practitioner supplies us with antibiotics when our immune system is not coping well or rapidly enough to clear an infection.

In livestock, particularly in pig, cattle and poultry farms, closely related antibiotics are used to prevent disease outbreaks and at amounts that surpass the use of antibiotics in humans. The use of antibiotics in animals and their accumulation in the environment potentially drives the development of antibiotic resistance. Already, superbugs have emerged, resistant to all antibiotics known to mankind. Alternatives to veterinary antibiotics are needed to control disease outbreaks in livestock and to reduce antibiotics use.

A promising approach is to boost the animal’s innate immune system and so elevate the threshold above which infections occur. The advantage of this approach is that the immune stimulants used to boost the immune system do not directly kill the bacteria; thus, do not drive resistance development. The potential of using immunoglobulins and host defense peptides to boost the immune system of livestock was presented by us and others during the “Second International Symposium on Alternatives to Antibiotics” in Paris, 2016 and extensively described in a recent review in Veterinary Research.

Immunoglobulins (Igs) are antibodies that ‘label’ foreign bacteria for uptake and digestion (phagocytosis) by immune cells. Besides natural transfer and protection via breast milk, Igs can be used for passive immunization of livestock. Licensed Ig-based products are already used to protect against bacterial infections, bacterial toxins and, for instance, West Nile virus in horses.

In comparison to Igs, host defense peptides (HDPs) are small (<100 amino acids often positively charged peptides that act via multiple antimicrobial mechanisms and therefore have a low risk of inducing antimicrobial resistance). In addition to broad-spectrum antimicrobial activities (bacteria, fungi, parasites and viruses) HDPs have a capacity to modulate immune cells.

© Albert van Dijk
© Albert van Dijk

Figure 1: Host defense peptides may induce innate immune memory of monocytes and macrophages and increase the threshold above which infection occurs.

 

 

 

HDPs can be used in different ways. Endogenous HDP expression can be stimulated with feed additives, e.g. short-chain fatty acids or probiotics or enhanced via breed selection or transgene approaches. In addition, HDPs can be used as templates for development of new antimicrobials and immunomodulators, as vaccine adjuvants or as an adjunct to antibiotic therapies.

A prime example of the prophylactic use of HDPs in livestock to prevent infections is the ‘in ovo’ immunomodulation in poultry. In chicken, in ovo HDP treatment was shown to reduce the mortality, the number of sick birds and the severity of illness caused by a bacterial infection. Postnatal prevention with HDP-derived ‘IDRs‘ (Immune Defense Regulators) were effective against invasive and systemic bacterial infections in animal models. As an adjunct to antibiotic therapy, HDPs were shown to improve the clinical outcome in mouse models of tuberculosis, cerebral malaria and systemic bacterial infection.

Our work resulted in several patents and we continue to study the mechanisms of action of HDPs as immunomodulators and as vaccine adjuvants. In conclusion, innate host defense mechanisms offer new strategies to treat and prevent microbial infections and disease in animal husbandry.

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