Metabolomics of Stress: Assessing Bio-Fluids in Rats and Humans using Proton Nuclear Magnetic Resonance (1H NMR) Spectroscop

Stress in utero causes epigenetic changes that manifest in offspring physiology and behaviour, becoming risk factors for complex adult diseases. Here we used 1H NMR spectroscopy to analyze two novel cohorts; first, we assessed urine metabolomes of adolescents in utero during the largest natural disaster in Canadian history; second, we investigated blood plasma metabolomes of offspring that were transgenerationally or multigenerationally-stressed in utero. Metabolomic profiles in offspring of high PNMS mothers were significantly altered. Higher PNMS generated significant alterations in metabolic pathways involving energy metabolism and protein biosynthesis in both rats and humans, particularly in BCAA synthesis, TCA cycle, muscle performance, and immunoregulation. Dysregulation of energy and protein metabolism suggests an increased risk of metabolic diseases, such as insulin resistance, diabetes, and obesity. The present findings provide a novel approach to PNMS outcomes and HPA-axis dysregulation by taking a metabolomics perspective and utilizing novel stressors in animal and human models.