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Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS.

ABSTRACT: Hydrophilic interaction-ultra high performance liquid chromatography (HILIC-UHPLC) allows the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP) chromatography. By optimization of the preparation and analytical conditions in HILIC mode, HILIC-UHPLC/MS was applied for the global metabolic profiling of rat plasma samples generated in an experimental model of chronic unpredictable mild stress (CUMS), and the concomitant investigation of the protective effect of fluoxetine was also evaluated. Identification of plasma metabolic profiles indicated that significant changes in specific metabolites occurred after fluoxetine exposure, including increased phenylalanine, serine, acetyl-L-carnitine, carnitine and decreased creatine, betaine, proline, tryptophan, tyrosine, C16:0 LPC. Some novel biomarkers from this HILIC-UHPLC/MS approach were betaine, proline, tyrosine creatine and serine compared with the results of RP-UHPLC/MS. The complementary nature of this technique is confirmed and is on agreement with previously published studies.

SUBMITTER: Zhao L

PROVIDER: S-EPMC4469692 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS.

Zhao Longshan L Xiong Zhili Z Lu Xiumei X Zheng Shuning S Wang Fang F Ge Lin L Su Guangyue G Yang Jingyu J Wu Chunfu C

PloS one 20150616 6

Hydrophilic interaction-ultra high performance liquid chromatography (HILIC-UHPLC) allows the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP) chromatography. By optimization of the preparation and analytical conditions in HILIC mode, HILIC-UHPLC/MS was applied for the global metabolic profiling of rat plasma samples generated in an experimental model of chronic unpredictable mild stress (CUMS), and the concomitant investigation of the protective e ...[more]

PMID: 26080063

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Project description:Antidepressant medications are known to modulate the central nervous system, and gut microbiota can play a role in depression via microbiota-gut-brain axis. But the impact of antidepressants on gut microbiota function and composition remains poorly understood. Thus this study assessed the effect of serotonin reuptake inhibitor antidepressant fluoxetine (Flu) and tricyclic antidepressant amitriptyline (Ami) administration on gut microbiota composition, diversity, and species abundance, along with microbial function in a chronic unpredictable mild stress (CUMS)-induced depression rat model. Oral administration of Ami and Flu significantly altered the overall gut microbiota profile of CUMS-induced rats, as assessed using the permutational multivariate analysis of variance test. At the phylum level, 6-week of antidepressant treatment led to a decreased Firmicutes/Bacteroidetes ratio due to an enhanced Bacteroidetes and reduced Firmicutes relative abundance. Flu was more potent than Ami at altering the Firmicutes and Bacteroidetes levels in the CUMS rats. At the family level, both antidepressants significantly increased the abundance of Porphyromonadaceae. However, an increased Bacteroidaceae level was significantly associated with Ami, not Flu treatment. Furthermore, at the genus level, an increase in the relative abundance of Parabacteroides, Butyricimonas, and Alistipes was observed following Ami and Flu treatment. Subsequent metagenomics and bioinformatics analysis further indicated that Ami and Flu likely also modulated metabolic pathways, such as those involved in carbohydrate metabolism, membrane transport, and signal transduction. Additionally, both antidepressants affected antibiotic resistome, such as for aminoglycoside (aph3iiiA), multidrug (mdtK, mdtP, mdtH, mdtG, acrA), and tetracycline (tetM) resistance in CUMS rats. These data clearly illustrated the direct impact of oral administration of Flu and Ami on the gut microbiome, thus set up the foundation to reveal more insights on the therapeutic function of the antidepressants and their overall contribution to host health.

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Dataset Information

Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS.

Publications

Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS.

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