Phospholipid profiling of plasma from GW veterans and rodent models to identify potential biomarkers of Gulf War Illness

Gulf War Illness (GWI), which affects at least one fourth of the 700,000 veterans deployed to the Gulf War (GW), is characterized by persistent and heterogeneous symptoms, including pain, fatigue and cognitive problems. As a consequence, this illness remains difficult to diagnose. Rodent models have been shown to exhibit different symptomatic features of GWI following exposure to particular GW agents (e.g. pyridostigmine bromide, permethrin and DEET) and/or stress. Preclinical analyses have shown the activation of microglia and astroglia as a pathological hallmark in these mouse and rat models. Although much has been learned in recent years from these different rodent models and independent clinical studies, characterization studies to identify overlapping features of GWI in animals and humans have been missing. Thus, we aimed to identify biomarkers that co-occur in the plasma of rodent models of GWI and human GWI patients. We observed increases of multiple phospholipid (PL) species across all studied cohorts. Furthermore, these data suggested dysfunction within ether and docosahexaenoic acid and arachidonic acid containing PL species in relation to GWI. As these PL species play a role in inflammatory processes, these findings suggest a possible role for inflammatory imbalance in GWI. Overall, we show that the peripheral lipid disturbances are present both in human GWI patients and in the preclinical rodent models of GWI, highlighting the importance of lipidomics as a potential platform for further biomarker discovery and supporting the value of GW agent exposed models of GWI.