Dataset Information

Short Term Intrarectal Administration of Sodium Propionate Induces Antidepressant-Like Effects in Rats Exposed to Chronic Unpredictable Mild Stress.

ABSTRACT: Depression has been correlated with metabolic disorders, and the gut microbiota and its metabolites have been reported to be key factors affecting metabolic disorders. Several metabolites generated by the gut microbiota have been reported to exert antidepressant-like effects, including the short chain fatty acid (SCFA) butyrate. However, recent work has suggested that the abundance of butyrate is not significantly changed in neither human nor experimental animals with depression, and butyrate has been reported to decrease upon the administration of prebiotics with antidepressant-like effects. Supplementation of endogenous metabolites that are unchanged in depression may induce additional metabolic disorders and may lead to poorer clinical outcomes. However, the endogenous metabolites that are imbalanced in depression may include several antidepressant candidates that could circumvent these problems. In this study, we used GC-MS spectrometry to study the fecal metabolome of rats under Chronic Unpredictable Mild Stress (CUMS). We carried out static and dynamic metabolomics analyses to identify the differential metabolites between the CUMS rats and control rats. We identified propionic acid, rather than butyric acid, as a differential metabolite of the CUMS rats. Consistent with this, a 1-week intrarectal administration of sodium propionate (NaP, the salt form of propionic acid) induced antidepressant-like effects and partially rebalanced the plasma metabolome. The antidepressant-like effects of NaP were correlated with differential rescue of neurotransmitters in the prefrontal cortex, which may be achieved through the reduction of catabolism of noradrenaline, tryptophan and dopamine, rather than serotonin. These findings support NaP as a potential candidate in fighting depression by administering an endogenous metabolite.

SUBMITTER: Li J

PROVIDER: S-EPMC6170646 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Short Term Intrarectal Administration of Sodium Propionate Induces Antidepressant-Like Effects in Rats Exposed to Chronic Unpredictable Mild Stress.

Li Jianguo J Hou Luwen L Wang Cui C Jia Xueyang X Qin Xuemei X Wu Changxin C

Frontiers in psychiatry 20180927

Depression has been correlated with metabolic disorders, and the gut microbiota and its metabolites have been reported to be key factors affecting metabolic disorders. Several metabolites generated by the gut microbiota have been reported to exert antidepressant-like effects, including the short chain fatty acid (SCFA) butyrate. However, recent work has suggested that the abundance of butyrate is not significantly changed in neither human nor experimental animals with depression, and butyrate ha ...[more]

PMID: 30319461

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Project description:Shugan Jieyu Capsule (SG) has been widely used in China to treat mild to moderate depression. Hypericum perforatum L. (St John's Wort, SJW) is the main ingredient of SG and has been used as herbal medicine to treat depression in western countries. However, it is known that SJW has low bioavailability and does not easily get through the blood-brain barrier. Therefore, how SG plays an antidepressant effect in the central nervous system (CNS) remains an urgent problem to be solved. Mounting research has described the relationship between antidepressants and intestinal microbiota to illuminate antidepressive mechanisms in the CNS. We aimed to investigate the effects of therapy with SG on the function of gut microbiota and intestinal microbiota in rats with chronic unpredictable mild stress (CUMS)-induced depression. The psychophysiological state and the hypothalamic-pituitary-adrenal axis function of rats are evaluated through behavioral experiments, corticosterone levels, serotonin levels, and adrenal index measurements. 16S rDNA amplicon sequencing is used to test the changes in gut microbiota and make functional predictions of genes. With treatment of SG, the depression-like behaviors of CUMS-induced rats were reversed; the corticosterone levels and the adrenal index decreased significantly; the level of serotonin increased significantly; and the alpha and beta diversity analysis of microbiota showed an increase in the richness and uniformity of the flora were increased. SG regulated the relative abundance of Actinobacteria, Erysipelotrichaceae, Bifidobacteriaceae, Atopobiaceae, Dubosiella, and Bifidobacterium; Linear discriminant analysis effect size analysis demonstrated that Lactobacillaceae (family level), Lactobacillus (genus level), Lactobacillales (order level), Bacilli (class level), and Lactobacillus-reuteri (species level) were biomarkers in the SG group samples, and also likely to modulate metabolic pathways, such as those involved in carbohydrate metabolism, amino acid metabolism, and signal transduction. These data clearly illustrated the effect of SG on gut microbiome, thus laying the foundation for uncovering more insights on the therapeutic function of the traditional Chinese antidepressants. The potential of SG on mechanisms of antidepression to alter gut microbiota and intestinal microbiome function exposed to CUMS can be explored.

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.

Dataset Information

Short Term Intrarectal Administration of Sodium Propionate Induces Antidepressant-Like Effects in Rats Exposed to Chronic Unpredictable Mild Stress.

Publications

Short Term Intrarectal Administration of Sodium Propionate Induces Antidepressant-Like Effects in Rats Exposed to Chronic Unpredictable Mild Stress.

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