Abstract
Stress disorders have dramatically increased in recent decades becoming the most prevalent psychiatric disorder in the United States and Europe. However, the diagnosis of stress disorders is currently based on symptom checklist and psychological questionnaires, thus making the identification of candidate biomarkers necessary to gain better insights into this pathology and its related metabolic alterations. Regarding the identification of potential biomarkers, omic profiling and metabolic footprint arise as promising approaches to recognize early biochemical changes in such disease and provide opportunities for the development of integrative candidate biomarkers. Here, we studied plasma and urine metabolites together with metagenomics in a 3 days Chronic Unpredictable Mild Stress (3d CUMS) animal approach that aims to focus on the early stress period of a well-established depression model. The multi-omics integration showed a profile composed by a signature of eight plasma metabolites, six urine metabolites and five microbes. Specifically, threonic acid, malic acid, alpha-ketoglutarate, succinic acid and cholesterol were proposed as key metabolites that could serve as key potential biomarkers in plasma metabolome of early stages of stress. Such findings targeted the threonic acid metabolism and the tricarboxylic acid (TCA) cycle as important pathways in early stress. Additionally, an increase in opportunistic microbes as virus of the Herpesvirales was observed in the microbiota as an effect of the primary stress stages. Our results provide an experimental biochemical characterization of the early stage of CUMS accompanied by a subsequent omic profiling and a metabolic footprinting that provide potential candidate biomarkers.
Highlights
IntroductionPsychological stress disorders have dramatically increased in recent decades, becoming a prevalent global health problem
Introduction distributed under the terms andPsychological stress disorders have dramatically increased in recent decades, becoming a prevalent global health problem
Prolonged or repeated activation of the hypothalamic–pituitary–adrenocortical axis (HPA) and SAM systems can interfere with a broad range of physiological processes, resulting in an increased risk of non-communicable diseases (NCDs), cardiovascular diseases, in addition to the traditional psychiatric disorders related with stressful events [3]
Summary
Psychological stress disorders have dramatically increased in recent decades, becoming a prevalent global health problem. Nowadays, it affects the lives of almost 300 million people worldwide suffering from a range of different stress disorders [1]. Stressful events are thought to influence the pathogenesis of other non-communicable diseases (NCDs) by causing negative affective states (e.g., feelings of anxiety and depression) [2]. Prolonged or repeated activation of the HPA and SAM systems can interfere with a broad range of physiological processes, resulting in an increased risk of NCDs, cardiovascular diseases, in addition to the traditional psychiatric disorders related with stressful events [3]
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