Strain-specific Metabolomic and Inflammatory Profiles in Guinea Pigs After LPS-induced Inflammation: Comparative Analysis of Dunkin-Hartley and Trik 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 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.急性炎症（Acute inflammation）是由多种入侵病原体触发的复杂生物学应答，可激活不同的免疫通路。由于豚鼠（guinea pig）的品系间差异可影响炎症应答，最终改变疾病进程，因此解析这些品系特异性差异，可提升豚鼠模型在急性炎症研究中的可靠性与转化相关性。本研究选取两种豚鼠品系：Trik有色品系与Dunkin-Hartley白化品系，通过细菌内毒素脂多糖（lipopolysaccharide, LPS）诱导急性全身性炎症。本研究采用氢-1核磁共振（hydrogen-1 nuclear magnetic resonance, ¹H NMR）光谱技术，鉴定了血浆与支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中的特异性代谢物变化。血浆代谢组谱存在显著差异，表明在脂多糖诱导的急性炎症过程中，循环代谢物存在显著的品系间差异，涉及氨基酸转氨、氨转运以及免疫应答相关的代谢物。对脂多糖诱导炎症的豚鼠支气管肺泡灌洗液进行代谢组学分析，结果发现部分特异性代谢物水平出现下调。此外，本研究还评估了脂多糖暴露后，豚鼠血液与支气管肺泡灌洗液中的白细胞计数以及体重变化。在支气管肺泡灌洗液中，脂多糖可使Dunkin-Hartley品系的总细胞数出现轻微且无统计学意义的升高，同时中性粒细胞数显著增加。而在血液中，Trik品系的总白细胞数显著升高，中性粒细胞数则显著降低。两种品系的豚鼠均因脂多糖诱导出现体重下降，其中Trik品系的体重下降更为显著。本研究揭示了豚鼠脂多糖模型中的品系特异性代谢组学变化，强调了品系选择在炎症研究中的重要性。尽管本研究属于描述性研究，但这些初步发现为后续探索脂多糖的炎症机制、提升研究向人类疾病的转化价值提供了研究基础。