A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts

Area of Science:

• Neuroscience
• Biochemistry
• Military Medicine

Background:

• Military Breachers and Range Staff (MBRS) experience repeated sub-concussive blast exposures.
• These exposures are linked to symptoms consistent with mild traumatic brain injury (mTBI).
• Objective biomarkers are needed for blast injury diagnosis, surveillance, and prevention.

Purpose of the Study:

• To identify plasma metabolite biomarkers in military personnel exposed to repeated low-level or sub-concussive blast overpressure.
• To assess the diagnostic accuracy of these biomarkers for blast exposure.

Main Methods:

• 37 military members enrolled (18 MBRS, 19 controls) with varying blast exposure levels.
• Plasma metabolomics profiling was performed on all participants.
• Feature reduction and receiver operating characteristic (ROC) curve analyses were used to identify and validate biomarkers.

Main Results:

• Metabolomics profiling showed significant differences between MBRS and controls, with 74% classification accuracy.
• Six key metabolites (acetic acid, formate, creatine, acetone, methanol, glutamic acid) achieved 98% classification accuracy.
• Combinations of metabolites, particularly volatile organic compounds (VOCs), demonstrated high diagnostic accuracy (AUCs up to 1.00).

Conclusions:

• Candidate plasma metabolite biomarkers for chronic blast exposure were identified.
• These biomarkers, especially VOCs, show potential for aiding surveillance and care of military personnel.
• Future point-of-care screening using breath VOCs could be developed, with plasma metabolomics for definitive diagnosis.