Protected biofactors and antioxidants reduce the negative consequences of virus and cold challenge by modulating immunometabolism via changes in the interleukin-6 receptor signaling cascade in the liver

Authors: PERRY, FAMATTA - University Of Delaware; Johnson, Casey; LAHAYE - Jefo Nutrition Canada; SANTIN - Jefo Nutrition Canada; KORVER, D - University Of Alberta; Kogut, Michael - Mike; ARSENAULT, RYAN - University Of Delaware

Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/25/2024
Publication Date: 7/22/2024
Citation: Perry, F., Johnson, C.N., Lahaye, L., Santin, E., Korver, D.R., Kogut, M.H., Arsenault, R.J. 2024. Protected biofactors and antioxidants reduce the negative consequences of virus and cold challenge by modulating immunometabolism via changes in the interleukin-6 receptor signaling cascade in the liver. Poultry Science. 103(9). Article 104044. https://doi.org/10.1016/j.psj.2024.104044.
DOI: https://doi.org/10.1016/j.psj.2024.104044

Interpretive Summary: The poultry industry is searching for alternatives to in-feed antibiotic growth-promoters. Natural products and products that are protected from the harsh environment of the stomach are being tested for their beneficial effects on the growth and health of poultry. The liver of broiler chickens is an important organ for growth and for the processing of nutrients by the bird. In this study, the effects of two formulations of antibiotic alternatives on the function of the liver were measured and analyzed. Cold stress and a disease challenge (infectious bronchitis virus) were also used in this study to further understand the beneficial effects of these antibiotic alternatives. All birds were exposed to the cold stress and disease challenge. At day 15 post-hatch the birds were humanely euthanized, necropsied, and liver samples from the control and two supplement fed groups were taken and stored for later use. Chemical messengers and the effects that those messengers have on the cells that make up the liver were analyzed. Interleukin 6 is one chemical messenger that has an effect on immune responses and on how the cells of the liver process metabolic factors. Interleukin 6 and associated signaling were shown to be altered by the antibiotic alternatives being tested in this study. Both formulations tested here showed an overall anti-inflammatory effect in the face of the cold stress and disease challenge. The results here show that these alternatives to antibiotics have the potential to benefit the broiler industry by improving the response of chickens to stressors and ultimately aid in creating a safe and wholesome food supply for the consumer.

Technical Abstract: Protected biofactors and antioxidants (P(BF+AOx)), and protected biofactors and antioxidants with protected organic acids and essential oils (P(BF+AOx)+P(OA+EO)) have been shown to have benefits in stressed or challenged birds. Here, we describe the immunometabolic changes observed in the liver of Ross 308 broilers during feed supplementation and brief physiological stress. These biofactors and antioxidants contain oils and vitamins which may have protective effects on the liver. Thus, we aim to elucidate the signaling changes induced by these supplements and the resultant immunometabolic effects on the liver. All birds received a 2X dose of live bronchitis vaccine at day 0 and a 48 hour cold challenge by reducing the temperature from 30-32°C to 20-23°C on days 3-5. Control birds were fed standard diet without supplementation. Samples were collected to evaluate the effects of these treatments on cytokine gene expression and protein phosphorylation via kinome peptide array. ANOVA was used for statistical analysis of the gene expression data (p-value of 0.05), and PIIKA2 was used for statistical evaluation and comparative analysis of the kinome peptide array data. At day 15, the kinome peptide array analysis and gene expression showed stimulation of the interleukin 6 receptor (IL-6R) signal transduction for host protection via heightened immune response while inducing immune modulation and reducing inflammation in both supplement treated groups. Significant changes were observed via IL-6R signaling in the metabolic profiles of both groups compared to control and no significant differences when compared to each other. In the liver, these two feed additives induced immunometabolic changes predominantly via the IL-6 receptor family signaling cascade.