Strain-specific metabolomic and inflammatory profiles in guinea pigs after LPS-induced inflammation: Comparative analysis of Dunkin-Hartley and Trik strains.

Abstract

Acute inflammation is a complex biological response triggered by various invading agents provoking distinct immune pathways. As inter-strain variability in guinea pigs can influence inflammatory responses, ultimately affecting disease progression, understanding these strain-specific differences can improve the reliability and translational relevance of guinea pig models for studying acute inflammation. In this study, two guinea pig strains, Trik coloured and Dunkin-Hartley albino, were subjected to bacterial endotoxin lipopolysaccharide (LPS) to induce acute systemic inflammation. Specific metabolite alterations in the blood plasma and bronchoalveolar lavage fluid (BALF) were identified using hydrogen-1 nuclear magnetic resonance (¹H NMR) spectroscopy. Distinct differences in the metabolomic profiles in the blood plasma indicated significant inter-strain variability in circulating metabolites during LPS-induced acute inflammation, including those involved in amino acid transamination, ammonia transfer, and immune responses. Metabolomic analysis of BALF from guinea pigs with LPS-induced inflammation revealed decreased levels of specific metabolites. Moreover, changes in blood and BALF white blood cell counts and body weight were evaluated after LPS exposure. In BALF, LPS caused a slight, non-significant increase in total cell count and a significant neutrophil increase in the Dunkin-Hartley strain. In blood, Trik strain showed a significant increase in total count of cells and a significant neutrophil decrease. LPS induced weight loss in both strains, more pronounced in Trik. The study points out strain-specific metabolomic changes in guinea pig LPS model, highlighting the importance of strain selection in inflammation research. While descriptive, these preliminary findings provide a basis for future work to explore inflammatory mechanisms of LPS and improve translation to human disease.