Metabolomics in Gulf War Illness: A Systems Biology Approach to Dissecting Mechanisms of Disease

Scientific Objective and Rationale:

Nearly three decades after the 1990-91 Gulf War (GW), approximately 250,000 U.S. Veterans are estimated to be chronically disabled by GW Illness (GWI). Organophosphate pesticides, sarin gas, pyridostigmine bromide, depleted uranium, smoke from burning oil wells, multiple vaccinations, and combinations thereof, are attributed, but unconfirmed, to the pathophysiology of GWI, and there are no approved diagnostic biomarkers or treatments. This project will recruit Dr. W. Ian Lipkin from The Center for Infection and Immunity (CII) at Columbia University, a new investigator for GWI research, who has worked to decipher the challenges of similar complex chronic diseases.

The team will use a powerful method known as metabolomics: the analysis of small molecules (metabolites) that are part of normal human metabolism function. Through the use of metabolomics, we will investigate whether GWI is associated with abnormalities in blood levels of metabolites that in turn reflect disturbances in the function of specific organs or tissues. We will test blood samples obtained in a rested state from 100 GW Veterans with GWI and compare them to 100 GW Veterans without GWI. Metabolomic testing will also be used to analyze blood samples from 50 GW Veterans with GWI and compare them to 50 GW Veterans and civilians without GWI before and 24 hours after an exercise tolerance test (ETT). The ETT will highlight if physical exertion/stress causes metabolic changes and if these changes enhance the ability to find metabolic abnormalities that are not otherwise detectable from the rested state. These abnormalities can provide guidance on triggers of GWI and potential opportunities for diagnostics and treatment.

Applicability of Research:

Results of this project have the potential to yield new diagnostic tests for GWI, provide insights into the mechanisms of potential exposures that cause GWI, and suggest strategies for treatment. At the end of this project, the GWI metabolomic data will be compared to the libraries CII has on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-treatment Lyme disease (PTLD), which share multiple symptoms and similarities with GWI. Comparing these three datasets allows for any overlapping patterns to emerge and would strengthen the chance of advancing the GWI research field. While the disease-inducing events may be different between GWI, ME/CFS, and PTLD, similar changes in metabolites can exist and provide insight into the systemic symptoms being experienced.

This project will utilize samples already acquired from GW Veterans, so there will be no additional risks to the population. Additionally, this project is based on a 3-year timeline. It is anticipated that at the project's conclusion, a plan for next stage of research towards clinical and diagnostic aims will begin to take shape. Within the first year of Lipkin's Center for Solutions for ME/CFS work, a preliminary test based on metabolomic analysis had been developed with an 84% effective rate for ME/CFS diagnosis. By harmonizing the data analysis over these three chronic illnesses, we believe the ability to achieve a similar solution with GWI is possible.