medRxiv : the preprint server for health sciences · 2026
The Metabolomic Signature of Stressful Life Events.
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Tian Yumeng, Li-Gao Ruifang, Alshehri Tahani, Brydges Christopher R, Arnold Matthias, Mahmoudiandehkordi Siamak, Kastenmüller Gabi, Mook-Kanamori Dennis O, Rosendaal Frits R, Giltay Erik J, Xu Lin, Wang Jiao, Jansen Rick, Bastiaanssen Thomaz, Penninx Brenda W J H, Kaddurah-Daouk Rima, Milaneschi Yuri
Аннотация
Stressful life events impact individual's functionality and contribute to disease outcomes, yet the biological pathways underlying life stress remain unclear. We characterized the metabolomic profiles of stressful life events using data from 3,264 participants (5,163 observations) of the Dutch NESDA cohort. 98 metabolites were identified, with upregulated metabolites overrepresented in phosphatidylethanolamine and downregulated metabolites overrepresented in fatty acid metabolism. 92 of these metabolites were available in the Dutch NEO cohort (N=599): 11 were significantly replicated including six lipids (e.g., three bile acids (glycochenodeoxycholate 3-sulfate)), one carbohydrate, and one xenobiotic. 21 overlapping metabolites were additionally available in the Chinese GBCS cohort (N=200): 10-undecenoate (11:1n1) (fatty acid) and glycochenodeoxycholate 3-sulfate (bile acid) showed consistent associations across both Dutch and Chinese cohorts. Stressful life events are associated with metabolic dysregulation, particularly involving fatty acid and bile acid pathways, highlighting promising biological targets to reduce the impact of stress on mental and somatic health.