Mycotoxins produced by fungal species commonly contaminate livestock feedstuffs, jeopardizing their health and diminishing production. Citrinin (CIT) and ochratoxin A (OTA) are mycotoxins produced by Penicillium spp. and commonly co-occur. Both CIT and OTA can modulate immune response by inhibiting cell proliferation and differentiation, altering cell metabolism, and triggering programmed cell death. The objective of this study was to determine the effects of sublethal exposure (i.e., the concentration that inhibited cell proliferation by 25% (IC₂₅)) to CIT, OTA or CIT + OTA on the bovine macrophage transcriptome. Gene expression was determined using the Affymetrix Bovine Genome Array. After 6 h of exposure to CIT, OTA or CIT + OTA, the number of differentially expressed genes (DEG), respectively, was as follows: 1471 genes (822 up-regulated, 649 down-regulated), 5094 genes (2611 up-regulated, 2483 down-regulated) and 7624 genes (3984 up-regulated, 3640 down-regulated). Of these, 179 genes (88 up-regulated, 91 down-regulated) were commonly expressed between treatments. After 24 h of exposure to CIT, OTA or CIT + OTA the number of DEG, respectively, was as follows: 3230 genes (1631 up-regulated, 1599 down-regulated), 8558 genes (4167 up-regulated, 4391 down-regulated), and 10,927 genes (6284 up-regulated, 4643 down-regulated). Of these, 770 genes (247 up-regulated, 523 down-regulated) were commonly expressed between treatments. The categorization of common biological functions and pathway analysis suggests that the IC₂₅ of both CIT and OTA, or their combination, induces cellular oxidative stress, a slowing of cell cycle progression, and apoptosis. Collectively, these effects contribute to inhibiting bovine macrophage proliferation.

Previous study indicated that inclusion of an algae-based antioxidant as an antioxidative agent [EconomasE, Alltech, Nicholasville, KY; EcoE] significantly reduced the amount of vitamin E (VE) required in broiler diets without compromising performance and meat quality. To assess the mechanisms related to the VE-saving activity of EcoE, as well as other potential functions related to EcoE and VE supplementation, we analyzed gene expression profiles of breast muscle from broilers fed a control diet, the control diet + 50 IU of VE/kg, the control diet + 100 IU of VE/kg, or the control diet + 200 g of EcoE/ton. Evaluation of the serum antioxidant capacity indicated that dietary supplementation of either a high level of VE (50 or 100 IU of VE/kg) or EcoE significantly improved bird antioxidant status. Analysis of gene expression profiles indicated that expression of 542 genes of the breast muscle were altered (P < 0.05, fold change >1.2) by dietary treatments, of which a significant part were commonly regulated by EcoE and VE (especially the control diet + 50 IU of VE/kg). In addition to the process of cellular oxidation, gene ontology analysis indicated the involvement of EcoE and VE on cell morphology, skeletal and muscular system development and function, immune response, and multiple metabolic processes, including lipid, carbohydrate, and drug metabolism. Results of this experiment indicate that the biological roles of high VE, including its activity as an antioxidant, can be greatly mimicked at the transcriptional level by EcoE, and they suggest a relationship of functional redundancy between VE and EcoE in the broiler diets.

1. The addition of yeast cell wall (YCW) mannan fractions or low concentrations of antibiotics to the diet of broilers positively affects gut health by improving intestinal cell morphology and improves feed efficiency and performance; however the exact mechanisms are unclear. Based on these production responses, the objective of this study was to compare the effects of supplementing YCW and bacitracin methylene disalicylate (BMD) in the diet on mRNA levels in the jejunum of 6-week-old broilers. 2. Dietary treatments were a maize-soya control diet and the control diet with the addition of YCW or BMD. Birds (n = 7) from each dietary treatment were randomly selected and killed at d 42. Whole jejunum (with serosa) samples were collected for RNA isolation. Gene expression analysis was performed using the AffymetrixGeneChip Chicken Genome Array (Santa Clara, CA, USA). 3. Supplementation with YCW resulted in 928 genes that were significantly changed (456 down-regulated, 472 up-regulated) and supplementation with BMD resulted in 857 genes that significantly changed (408 down-regulated, 449 up-regulated). In addition, 316 genes were significantly changed by both YCW and BMD (146 down-regulated, 170 up-regulated). 4. BMD increased the expression of genes involved in lipid and carbohydrate metabolism and decreased expression of genes associated with T-helper cell pathways. Gene expression profiles from birds fed on diets containing YCW showed changes on a genomic level that correspond to slower gut cell turnover and therefore increased energy preservation for growth. 5. In conclusion, supplementation with BMD or YCW had similar influences on the number of differentially expressed genes in the jejunum. Biological functions common to both YCW and BMD with positive activation scores included antiviral response and antimicrobial response. Genes that were affected by BMD or YCW classified into both different and common biological functions and pathways related to improved metabolism and health in the jejunum.