Transcriptome Analysis Reveals a Differential Gene Regulation Pattern By Antibiotic Growth Promoter in the GIT of Calves As Compared to Lactobacillus acidophilus and Saccharomyces cerevisiae

Antibiotic growth promoters (AGP) have been routinely used to enhance farm animal performance but problems associated with the development of antibiotics resistance has necessitated the search for alternatives. This study aimed to determine the mechanism of action of AGP as compared to Lactobacillus acidophilus (LA) and Saccharomyces cerevisiae (SC) in calf growth. Thirty-two calves (~5 days old) were separated equally into four groups: Control (CTL)- milk replacer+starter diet (from third week); CTL+LA BT1386 (2.5x10⁸ cfu/L milk replacer+1x10⁹cfu/kg feed); CTL+SC boulardii CNCM I-1079  (7.5x10⁸ cfu/L milk replacer+3x10⁹cfu/kg feed); and CTL+tetracycline (528mg/L)/neomycin (357mg/L) and chlortetracyclin (55mg/kg) . Sixteen calves were euthanized on day33 (pre-weaning) and another 16 on day96 (post-weaning) for the collection of rumen and ileum tissues. Total RNA was subjected to mRNA sequencing.

Bioinformatics processing of data showed that 17296 genes were expressed. 1196 and 3605 genes were differentially expressed (DE) between day33 and 96 for ileum and rumen tissues, respectively. Most DE genes in rumen included ATP12A (fold change [FC]=-28.86), LY6D (FC=-27.67), SLC26A9 (FC=-25.83) and TRIM55 (FC=17.61) and in Ileum MT1A(FC=-13.38), ISG15(FC=-7.64) and CYP1A1(FC=7.43). Ten, 131 and 7 genes were DE between LA vs. CTL, ATB vs. CTL, and SCB vs. CTL, respectively. RDH16, involved in retinol metabolism, signal transduction and metabolic pathways was DE between all treatments and CTL. Pathway analyses of DE genes between day33 and 96 shows enrichment in functions such as: cellular development/movement, growth/proliferation, cell death/survival/lipid metabolism. Genes DE between ATB vs. CTL were enriched in immune related functions (response to stimulus, immune system/cellular/metabolic process and biological regulation) and pathways of differential regulation of cytokine production, inflammation mediated response, interleukin and Wnt signalling. DE genes between day33 and 96 are involved in growth and developmental processes. Data show that ATB enhances health and growth of calves differently than SCB and LA. More studies are needed to further understand how ATB enhances health and growth of calves to facilitate the search for a suitable alternative.