Proteomic and Lipidomic Plasma Evaluations Reveal Biomarkers for Domoic Acid Toxicosis in California Sea Lions

Domoic acid is a neurotoxin secreted by the marine diatom genus Pseudo-nitzschia during toxic algal bloom events. California sea lions (Zalophus californianus) are exposed to domoic acid through the ingestion of fish that feed on toxic diatoms, resulting in domoic acid toxicosis (DAT), which can vary from mild to fatal. Sea lions with mild disease can be treated if toxicosis is detected early after exposure. Therefore, rapid diagnosis of DAT is essential but also challenging. In this work, we performed multiomics analyses, specifically proteomic and lipidomic, on blood samples from 31 California sea lions. Fourteen sea lions were diagnosed with DAT based on clinical signs and post-mortem histological examination of brain tissue, and 17 had no evidence of DAT. Proteomic analyses revealed 31 statistically significant proteins in the DAT individuals compared to the non-DAT individuals (adjusted p p 1) in the DAT versus non-DAT comparison. Of these, 28 were lower in the DAT individuals, while only 1 was higher. Furthermore, 15 of the 28 lower concentration lipids were triglycerides, illustrating their putative connection with the perturbed apolipoproteins and potential use in rapid DAT diagnoses.软骨藻酸（domoic acid）是一种由海洋硅藻属拟菱形藻（Pseudo-nitzschia）在有毒藻华事件中分泌的神经毒素。加州海狮（Zalophus californianus）可通过摄食以有毒硅藻为食的鱼类接触软骨藻酸，进而引发软骨藻酸中毒（DAT），病情轻重程度不一，可从轻微症状发展至死亡。轻症海狮若在暴露后早期检出中毒，即可接受治疗。因此，快速诊断软骨藻酸中毒具有重要意义，但同时也颇具挑战。本研究对31头加州海狮的血液样本开展了多组学分析，具体包括蛋白质组学（proteomic）与脂质组学（lipidomic）分析。根据临床症状及脑组织死后组织病理学检查结果，其中14头海狮被确诊为DAT，剩余17头未检出DAT相关证据。蛋白质组学分析显示，与非DAT组海狮相比，DAT组海狮体内存在31个统计学显著差异蛋白（校正后p值<0.05），其中28个蛋白在DAT组中的表达水平更低，仅1个蛋白表达水平更高。此外，脂质组学分析中28个在DAT组中浓度显著降低的脂质里，有15种为甘油三酯（triglycerides），这表明它们与紊乱的载脂蛋白（apolipoproteins）存在潜在关联，或可用于快速诊断DAT。