Dietary supplementation of lactoferrin in poultry

The growing global population has led to more demand for animal protein and a shift from extensive to intensive poultry farming systems. Intensive poultry farming increases the prevalence of diseases such as necrotic enteritis, and the application of antibiotics for prophylactic and growth promotion purposes. Excessive antibiotic use leads to a rise in antimicrobial-resistant bacteria, residues in animal products, environmental contamination, and poses a public health hazard. Potential antibiotic alternatives include probiotics, prebiotics, nutraceuticals, and plant extracts. Researchers set out to determine the potential of lactoferrin.

The properties of lactoferrin

Lactoferrin, a multifunctional, single polypeptide chain glycoprotein with about 690 amino acid residues, is present in secretory fluids such as mucus, breast milk, tears, saliva, and secondary granules of neutrophils and blood. Lactoferrin has a 60% sequence similarity to serum transferrin, and it exists in 3 distinct isoforms. Lactoferrin-α is the iron-binding form, and lactoferrin-β and lactoferrin-γ demonstrate ribonuclease activity but cannot bind iron.

Lactoferrin improves the body’s ability to absorb iron, prevents the formation of many hazardous chemicals, modulates cell development, and neutralises free radicals. Because lactoferrin is mainly present in mucosa and external secretions, it plays a significant role in non-specific immune response. In addition, lactoferrin has antioxidant, antibacterial, anti-inflammatory and antiviral properties and it stimulates the proliferation of lymphocytes, thus contributing to systemic and mucosal immune defenses.

Antibacterial activity of lactoferrin

Lactoferrin has natural antibacterial properties through its hydrolysate, and antimicrobial peptides that prevent colony formation of bacteria such as Staphylococcus mutans, Streptococcus epidermidis, and E. coli. Iron is essential for the growth of many bacteria including Listeria monocytogenes, Salmonella, E. coli and Bacillus subtilis; however, lactoferrin binds to iron and deprives bacteria of this essential nutrient and interferes with the cell receptors of pathogenic microorganisms and the cells of their hosts. Furthermore, lactoferrin is a non-toxic, natural antibacterial preserving dairy, meat, seafood, beverages, and bakery products. Lactoferrin improves the protection of chickens against Salmonella pullorum infection and increases the levels of IgG in the serum and IgA in the gut mucus.

Antioxidant activity of lactoferrin

Daily supplementation with lactoferrin significantly reduces the high plasma hydrogen peroxide and the generation of reactive oxygen species and promotes immune system responses via antioxidative processes. The antioxidant activity of lactoferrin is due to radical scavenging, reducing capabilities, and the ability to chelate divalent pro-oxidant metals.

Anti-inflammatory activity of lactoferrin

Lactoferrin plays an important role in immune protection and mucosal defense systems and prevents the production of inflammatory cytokine and the ability of lipopolysaccharide endotoxins to bind to inflammatory cells. In addition, lactoferrin blocks allergens, decreases the intensity of localised cutaneous inflammatory reactions, promotes systemic immunity, and functions as a robust anti-inflammatory protein in local areas of inflammation such as the digestive and respiratory tracts.

Antiviral activity of lactoferrin

Lactoferrin creates an iron-deficient environment by chelating iron to prevent microorganisms’ proliferation. In addition, lactoferrin binds to certain DNA and RNA viruses, the glycosaminoglycans on the surface of the host cell membrane, and viral particles. Lactoferrin controls infection at an early stage by preventing viruses from entering cells. This makes it a valuable strategy for novel viral infection treatments.

Immunomodulatory activity of lactoferrin

Neutrophil cytoplasmic granules, an integral part of the innate and adaptive immune responses, comprise the iron-free form of lactoferrin and destroy ingested pathogens. During inflammation, lactoferrin is released and its concentration enhances from 0.4-2.0 g/mL to 200 g/ mL. Lactoferrin modulates the immune system through interactions with epithelial and immune cell specific receptors. In addition, dietary supplementation with lactoferrin enhances the immune response due to its antioxidant properties and regulates lymphocyte subsets of broilers. Lactoferrin treatment in poultry boosts cell-mediated immunity, improves Infectious Bursal Disease vaccination disease resistance, and increases the serum IgG titre.

Iron absorption activity of lactoferrin

Iron is an essential mineral that is required for key enzymes in different metabolic pathways and cellular activities in poultry. Iron deficiency leads to fatigue and a reduction in immune system function. On the other hand, excessive dietary iron increases the formation of free oxygen radicals. Lactoferrin regulates iron absorption in the poultry gut, and maintains iron balance in the normal range to avoid iron deficiency or excessiveness.

Biomarker activity of lactoferrin

A biomarker is described as an objective measure of normal biological processes, pathogenic processes or responses to an exposure or intervention. Biomarkers are categorised as diagnostic, monitoring, pharmacodynamic, prognostic and predictive. Biomarkers are used for early-stage diagnosis, understanding disease prediction, cause, progression, regression, or outcome. Lactoferrin found in faecal, serum, tears and other secretions from the body can be used as an indicator of gut inflammatory diseases. In addition, dietary supplementation of lactoferrin modifies gut microbial profiles, increases the height of the gut villi, enhances the depth of the gut crypt, and improves nutrient absorption in broilers.

Lactoferrin and nanotechnology

In the poultry industry, nanotechnology is applied to improve production performance, weight gain, and feed conversion ratio. Lactoferrin can be combined with nanoparticles to develop novel and effective treatments. Nanoparticles interact with specific biologically active proteins; however, in combination with lactoferrin, nanoparticles have no effect on protein conformation. For example, feeding metronidazole-loaded lactoferrin nanoparticles enhances antitrichomonal activity in pigeons.

Nano-aggregation, which occurs whenever single nanoparticles cluster together to form larger objects, influences the technological application of nanoparticles. The nano-aggregation process improves the antimicrobial characteristics of lactoferrin by evenly distributing cationic charges on the surface of the polymer and enhancing interactions with anionic microbial membranes. In addition, antiviral particles can be placed inside lactoferrin. Furthermore, lactoferrin can be conjugated with inorganic nanoparticles which increases the loading capacity, biocompatibility and connection to ligands and effectiveness against Staphylococcus aureus infections.

The impact of lactoferrin on health and performance

Lactoferrin improves growth in poultry by increasing feed intake, improving nutrient utilisation and modulating the immune system by stimulating the production of cytokines and chemokines. Moreover, lactoferrin injection into the layer breeder eggs before incubation stimulates bone development and improves the bone strength and egg weight of laying hens at 28 weeks of age.

Concluding remarks

Genetically engineered lactoferrin has antibacterial, antioxidant, anti-inflammatory, antiviral, immunomodulatory, iron absorption and biomarker activities. Lactoferrin is a potential antibiotic substitute in poultry diets that improves growth performance, immune response, and gut health. However, further research is needed regarding the application of lactoferrin in poultry nutrition to acquire better knowledge of its function.

This article is based on a paper ‘The potential of lactoferrin: a call for future research in poultry nutrition’ published in the World’s Poultry Science Journal, August 2023