DOI: 10.1093/jas/skag272.186 ISSN: 0021-8812

146. Methionine Hydroxy Analogue Bis-Chelates Expedite Metabolic Recovery from an LPS Induced Inflammatory Challenge.

Jesus A Acosta Camargo, Laura Payling, Maria C Walsh, Bradley V Lawrence, Luis F Romero, Marisol Castillo, Deana Hancock

Abstract

An acute inflammatory response results in adverse metabolic events. Minerals play important roles in many of the metabolic processes associated with the inflammatory response, but the impact of trace mineral source is not well characterized. Therefore, this study was conducted to evaluate the impact of trace mineral source on a quantitative metabolic efficiency index (MEI; SAVVYTM Metabolic Efficiency Index, BIOFRACTAL, Portugal). Pigs were the experimental model. Diets were fed for 25-d prior to and through 72-hr post intramuscular lipopolysaccharide (LPS) intramuscular injection (15 ųg/kg body weight; E. coli O55:B5). Diets provided 80 mg/kg Zn, 20 mg/kg Cu and 40 mg/kg Mn either in the inorganic form (ITM; Zn and Mn as oxide; Cu as sulfate) or in the methionine hydroxy analogue bis-chelate (MHAC; MINTREX Trace Minerals) form. Diets contained 2,000 FTU/kg phytase. Blood samples were collected serially from 10 pigs per treatment via jugular venipuncture into Tempus™ RNA blood tubes immediately before LPS injection and at 6 and 72 hours post-injection. Sequencing of mRNA was performed (Illumina, 150 PE, globin depletion, 30M reads per sample) and gene abundance calculated (Kallisto). Differentially expressed genes were tested among treatments (Deseq2), followed by a topology-based Quantitative Pathway Activation method (QPA, BIOFRACTAL, Portugal) using an adj P < 0.05 threshold indicating relative pathway inhibition (QPA< 0) or activation (QPA >0). The transcriptomics-based MEI was used to quantify the effects of organic minerals from -100% (severe systemic challenge) to + 100% (optimum metabolic status) and 0 = no change relative to the reference. The LPS challenge resulted in metabolic collapse (MEI=-92%, adj P < 0.05) by 6-h post-LPS with some metabolic recovery by 72-h (-30%). Immediately prior to LPS, the MHAC pigs had a + 10% overall MEI (adj P < 0.05) compared with ITM driven by a lower immune system cost (MEI = +27%) and restorative tissue support and repair (MEI = +36%). The LPS resulted in metabolic collapse in both the ITM and MHAC pigs with a more robust response in the MHAC pigs (70%-vs. -82%). The more robust MHAC response was associated with a greater degree of oxidative stress (Oxidative balance and cellular health=-27%) compared with ITM. By 72-h, MHAC pigs recovered to a greater degree with an MEI = +12% vs. ITM driven by greater restoration of gut brain signaling (MEI = +27%), lower immune cost (MEI = +19%) and more restorative tissue support and repair (MEI = +52%). These results indicate that MHAC prior to an inflammatory challenge may result in a more robust initial response resulting in greater oxidative stress and a more rapid recovery particularly in gut-brain signaling and tissue support and repair. Using MHAC trace minerals in place of inorganic sources may enhance the animal’s ability to withstand and recover from inflammatory stress, improving overall metabolic efficiency and resilience.