The immunometabolic and molecular effects of potential antibiotic alternatives as feed supplements in broilers
| Author(s) | Perry, Famatta | |
| Date Accessioned | 2023-10-09T16:57:55Z | |
| Date Available | 2023-10-09T16:57:55Z | |
| Publication Date | 2023 | |
| SWORD Update | 2023-09-20T19:15:45Z | |
| Abstract | In this project, I aimed to expand our understanding of the immunometabolic effects and the mechanism of action of feed additives in broiler chickens’ gastrointestinal health. Poultry is the number one consumed meat in the world, thus improved production efficiency and health are important to feed the world. I determined the effects of 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)) on the immune and metabolic health of Ross 308 broiler chickens. In the jejunum, the kinome peptide array data analysis showed increased activity of cytoskeletal, cell growth and proliferation proteins, and metabolic signaling in the jejunum of P(BF+AOx)+P(OA+EO) treated chickens. There was a significant decrease in IL-6 gene expression in the jejunum of P(BF+AOx)+P(OA+EO) samples compared to control at day 15. P(BF+AOx)+P(OA+EO) treatments in the jejunum showed strong immunomodulatory effects, perhaps to control inflammation. P(BF+AOx)+P(OA+EO) improves gut health via growth and metabolic signaling in the jejunum while inducing stronger immunomodulation. While in the liver, 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 maintaining immunomodulation and reduction of damaging inflammation in both P(BF+AOx) and P(BF+AOx)+P(OA+EO) treated groups at day 15. Significant changes were observed via IL-6R signaling in the metabolic profiles of both groups when compared to control with no significant differences when compared to each other. These two feed additives induced immunometabolic homeostasis predominantly via the IL-6 receptor family signaling cascade in the liver. ☐ The effects of sodium butyrate (SB) on metabolism the gastrointestinal tract and immune cells were also studied. Using the kinome peptide array, I examined the proteomic effects of 0.1% SB supplementation in the jejunum and ileum of Cobb 500 broiler chickens at days 21 and 35. Using cell viability assays, we assessed the effects of treating HD11 cells with 1 mM to 16 mM SB at different time points (6, 18, 50 hours). Trypan blue exclusion assays showed no significant differences (p>0.05) in live cell counts between control (ctrl) and treated groups at 6 hours, nor between the number of dead cells in the ctrl versus treated groups for 6, 18 and 50 hrs. At 18 hours, there were more live cells in the ctrl group than the 8mM and 16mM SB groups. At 50 hours, there were more live cells in the ctrl group than the 4- and 16-mM SB groups. Alamar blue cell viability assay showed no statistical differences between the ctrl group and cells treated with 16 mM SB at 6 hours. The kinome peptide array results showed more changes in phosphorylation for reduced diets with SB supplementation in the jejunum (401 peptides) than control with SB supplementation (261 peptides). There were also differences in the number of proteins observed in cell growth regulatory pathways like mTOR and cellular senescence. The phosphorylation statuses of cell cycle proteins were assessed, activation of CDK2, Cyclin-D1, CDK9 and CDK6, phosphorylation of Cyclin E; deactivation of mTOR, CDK1 and CDK7 indicates active G1 phase but not M or S phase in day 21 groups. These results suggest that SB does not decrease cell viability but may lead to reduction in cell growth and/or halt cell proliferation overtime by inducing changes in the cell cycle regulation. In the ileum, the kinome peptide array results showed significant changes in proteins involved in the major metabolic pathways, that is, glycolysis, tricarboxylic acid cycle and beta oxidation. Further analysis showed increased activity of beta oxidation enzymes including hydroxyacyl-coenzyme A dehydrogenase and acetyl-CoA carboxylase. SB increases beta oxidation which may induce hypoxia in segments with larger microbial populations like the ileum, indicated by increased HIF-1 and PKC activity. This increased hypoxia can trigger inflammatory responses via immune and immunometabolic pathways such as T-cell and C-type lectin signaling pathways. These immunometabolic changes by butyrate in the gut indicate more complex dual processes can only be understood in the context of metabolic state. | |
| Advisor | Arsenault, Ryan | |
| Degree | Ph.D. | |
| Department | University of Delaware, Department of Animal and Food Sciences | |
| DOI | https://doi.org/10.58088/y8s0-re11 | |
| Unique Identifier | 1416342471 | |
| URL | https://udspace.udel.edu/handle/19716/33388 | |
| Language | en | |
| Publisher | University of Delaware | |
| URI | https://login.udel.idm.oclc.org/login?url=https://www.proquest.com/dissertations-theses/immunometabolic-molecular-effects-potential/docview/2869040493/se-2?accountid=10457 | |
| Keywords | Molecular effects | |
| Keywords | Feed supplements | |
| Keywords | Broilers | |
| Keywords | Antibiotic alternatives | |
| Keywords | Immune cells | |
| Title | The immunometabolic and molecular effects of potential antibiotic alternatives as feed supplements in broilers | |
| Type | Thesis |