Influence of postruminal casein infusion and exogenous glucagon-like peptide 2 administration on the jejunal mucosal transcriptome in cattle

Authors: TROTTA, RONALD - University Of Kentucky; SWANSON, KENDALL - North Dakota State University; Klotz, James; HARMON, DAVID - University Of Kentucky

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/7/2024
Publication Date: 8/15/2024
Citation: Trotta, R.J., Swanson, K.C., Klotz, J.L., Harmon, D.L. 2024. Influence of postruminal casein infusion and exogenous glucagon-like peptide 2 administration on the jejunal mucosal transcriptome in cattle. PLOS ONE. 19(8): e0308983. https://doi.org/10.1371/journal.pone.0308983.
DOI: https://doi.org/10.1371/journal.pone.0308983

Interpretive Summary: Cattle are typically finished on a high corn diet that contains high levels of carbohydrate (energy) or starch to allow for more growth and improved meat quality. Cattle are well equipped to digest carbohydrates in grasses in their foregut. When grain-based diets containing large amounts of starch are fed, large amounts of starch can escape the foregut and enter the small intestine for potential digestion. Because cattle were not originally designed to digest these levels of starch, it has been shown that cattle small intestinal starch digestion could be limited by inadequate pancreatic and/or intestinal carbohydrase enzymatic activity (proteins that aid in the breakdown of food) and is a possible area to improve production efficiency. The objective of this experiment was to use casein infusion (milk protein) and glucagon-like peptide 2 administration to study the gene expression pathways and functions of the absorptive surface of the small intestine. This work demonstrated that the casein treatment had a no significant effect on gene expression in the bovine small intestine. Samples from cattle that received the glucagon-like peptide 2 treatment; however, had several affected pathways involving growth of the intestinal lining, digestion of nutrients, nutrient absorption and metabolism, and the barrier function of the intestinal lining. These identified pathways could used to improve cattle growth and feed efficiency. This work will be primarily of interest to other researchers looking to improve the production efficiency of cattle.

Technical Abstract: The objective of the current study was to evaluate the effects of postruminal casein infusion and exogenous glucagon-like peptide 2 (GLP-2) administration on transcriptomic pathways and functions of the jejunal mucosa in cattle using next-generation RNA sequencing. Twenty-four Holstein steers [250 ± 23 kg body weight (BW)] received a continuous abomasal infusion of 3.94 g raw corn starch/kg of BW combined with either 0 or 1.30 g casein/kg of BW for 7 d. Steers received subcutaneous injections in two equal portions daily of excipient (0.5% bovine serum albumin) or 100 µg GLP-2/kg of BW per day. At the end of the 7-d treatment period, steers were slaughtered for collection of the jejunal mucosa. Total RNA was extracted from jejunal mucosal tissue, strand-specific cDNA libraries were prepared, and RNA sequencing was conducted to generate 150-bp paired-end reads at a depth of 20 M reads in each direction. Differentially expressed genes (DEG), KEGG pathway enrichment, and gene ontology enrichment between treatments were determined based on the FDR-corrected P-value. Postruminal casein infusion downregulated (padj < 0.05) 7 genes of the jejunal mucosa and did not result in any enriched KEGG pathways or gene ontologies. Exogenous GLP-2 administration upregulated (padj < 0.05) 667 DEGs, 26 KEGG pathways, 198 biological processes, 56 cellular components, and 60 molecular functions. Exogenous GLP-2 downregulated (padj < 0.05) 1101 DEGs, 14 KEGG pathways, 270 biological processes, 105 cellular components, and 46 molecular functions. Enrichment analyses revealed that exogenous GLP-2 administration affected several pathways involving mucosal growth, nutrient digestion, absorption, and metabolism, and intestinal barrier function. Results of the current study identified pathways affected by exogenous GLP-2 administration that could have implications for improved animal growth and feed efficiency in cattle. This research generated novel targets for future research to elucidate mechanisms of GLP-2-mediated responses in the jejunal mucosa.