Translational potential of guinea pig model with LPS-induced inflammation: metabolomic profiles of two strains

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 the inflammatory responses, ultimately affecting disease progression, understanding these strain-specific differences can improve the reliability and translational relevance of guinea pig models in 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 LPS-sensitised guinea pigs 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 sensitisation 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 sensitisation induced weight loss in both strains, more pronounced in Trik. LPS-induced inflammation causes different metabolomic changes in blood of two guinea pig strains, underlining the importance of choosing the appropriate model to improve the translational relevance.