PS3-19. Spatial Metabolomic Investigation of Bovine Hepatic Tissue in Response to Liver Abscesses.

Abstract

Hepatocytes are the functional cells of the liver, tasked with metabolizing macronutrients, detoxifying and filtering blood, producing bile, supporting the immune system, and storing essential nutrients. Liver abscesses (LA) destroy hepatocytes and trigger an inflammatory response that can cause reduced feed intake, decreased feed efficiency, and in severe cases, decreased hot carcass weight. Our study aimed to evaluate the metabolic function of liver tissue at specific distances from LA. Liver tissue cores were excised from abscessed livers (n = 80) at 0, 1, 3, and ³ 10 cm distal to the connective tissue capsule surrounding the LA. Untargeted primary metabolites were profiled using gas chromatography-mass spectrometry. Mixed models were used to evaluate differences in metabolite abundance distal to a LA. Differentially abundant metabolites were analyzed using MetaboAnalyst for pathway enrichment. The analysis did not identify any pathways that reached statistical significance (FDR ≥ 0.77). Forty-nine metabolites differed between tissue immediately adjacent to a LA (0 cm) and tissue 10 cm distal of the LA, with tissue ³ 10 cm distal from a LA considered healthy tissue. Concentrations of nine metabolites (β-glycerolphosphate, digalacturonic acid, ethanolamine, inositol-4-monophosphate, nicotinic acid, malic acid, saccharic acid, sorbitol, xylitol) increased (P ≤ 0.05) as distance increased from a LA. This phenomenon is likely driven by the localized 'metabolic sink' created by the infection, where concentrated bacteria actively consumed carbon and energy sources, specifically organic acids, as well as malic acid and sugar alcohols, such as sorbitol and xylitol, to fuel anaerobic fermentation. The rise in ethanolamine and β-glycerolphosphate distal to the LA may reflect the restoration on structural integrity of the extracellular matrix and normal phosphate metabolism, which are otherwise disrupted by membrane lysis and inflammatory enzymatic activity within the LA 'influence zone'. Ten metabolites (2-aminobutyric acid, 3-phosphoglycerate, alpha aminoadipic acid, cholesterone, hypotaurine, lactic acid, myo-insitol, thymine, trans-4-hydroxyproline, uracil) decreased (P ≤ 0.04) as distance increased from a LA. The gradient could be driven by the localized accumulation of metabolic by-products surrounding the LA necrotic core, where intense anaerobic fermentation leads to a buildup of lactic acid and 3-phosphoglycerate. Concurrently, destruction of host and microbial cells at the LA releases nucleosides and their breakdown products, such as uracil and thymine, and structural degradation markers such as trans-4-hydroxyproline. The proximal to distal decline of these compounds reflects the transition from an inflammatory zone, characterized by high oxidative stress and cellular lysis, to the homeostatic environment of healthy, vascularized liver parenchyma. Spatial metabolomic mapping reveals a distinct biochemical ”influence zone” surrounding the liver abscess, where reduced healthytissue metabolites and elevated inflammatory byproducts form a gradient that extends outward from the necrotic abscess edge into the distal healthy parenchyma.