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 < 0.05).
Of these proteins, 19 were decreased in the DAT group of which three
were apolipoproteins that are known to transport lipids in the blood,
prompting lipidomic analyses. In the lipidomic analyses, 331 lipid
species were detected with high confidence and multidimensional separations,
and 29 were found to be statistically significant (adjusted p < 0.05 and log2­(FC) < −1 or >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.