title: Metabotyping of biofluids reveals stress-based differences in gut permeability in healthy individuals.
abstract: Life stress promotes gut dysfunction, but underlying biochemical events are not well-understood. In the present study, we describe the metabolic events associated with background stress and its potential influence on the response to novel incoming stress stimulus in healthy subjects. A 15 min cold pain test was carried out in healthy men and women stratified according to low (LS; n = 21) and moderate background stress (MS; n = 9) during jejunal segmental perfusion. Cold pain induced a stronger psychological response in MS compared to LS subjects, but similar increases in heart rate and blood pressure. Urine and plasma were analyzed using 1H NMR-based metabonomics. Basal stress levels were imprinted in the metabolic profiles indicating different energy and lipid homeostasis. Cold pain increased gut permeability, as determined by mannitol and xylose levels, the response being greater in LS subjects. Moreover, the rate of plasma clearance of mannitol and xylose was dependent on background stress level and gender. In addition, cold pain modulated the levels of circulating ketone bodies, Krebs's cycle intermediates, glucose, and the glucogenic alanine and lactate, which brings further evidence of an alteration of energy homeostasis. Therefore, unravelling life stress with metabonomics may provide a system biology basis for the clinical management and therapeutic surveillance of gut health and disorders.
authors.affiliation: Bioanalytical Science Department, Metabonomics & Biomarkers Group, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Rezzi
authors.forename: François-Pierre
authors.initials: FP
authors.lastname: Martin
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Mar
authors.initials: M
authors.lastname: Guilarte
authors.forename: María
authors.initials: M
authors.lastname: Vicario
authors.forename: Laura
authors.initials: L
authors.lastname: Ramos
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lobo
authors.forename: Esteban
authors.initials: E
authors.lastname: Saperas
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Malagelada
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003080:Cold Temperature; D005260:Female; D006801:Humans; D007583:Jejunum / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008353:Mannitol / Q000097:blood; D055432:Metabolomics / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010146:Pain / Q000378:metabolism*; D010539:Permeability; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D013312:Stress, Physiological / Q000502:physiology*; D014994:Xylose / Q000097:blood
chemical_list: D008074:Lipoproteins; D008353:Mannitol; D014994:Xylose