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      Neuropsychiatric Disease and Treatment (submit here)

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      Possible association of Firmicutes in the gut microbiota of patients with major depressive disorder

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          Abstract

          Background

          Gut microbiota can affect human behavior and mood in many ways. Several studies have shown that patients with depression were also accompanied with gut microbiota disorder, in which Firmicutes are related to the protective function of intestinal barrier. In this study, we explore the changes and effects of Firmicutes in the patients with major depressive disorder (MDD).

          Method

          We recruited 54 subjects, including 27 patients with MDD. Fecal samples were collected for identification by 16S rRNA sequencing and bioinformatics analysis.

          Results

          The study shows that the alpha diversity indices of MDD patients are lower than those of the healthy controls. Firmicutes is the most significantly decreased phylum in the MDD samples. There are totally 13 taxonomic biomarkers with P-value <0.01 from Firmicutes. There are differences in 17 KEGG pathways between the two groups.

          Conclusion

          This study found that there is a significant disorder of gut microbiota in the patients with depression, in which the Firmicutes decreased significantly. Defects of the Firmicutes may lead to the depression in short-chain fatty acids, which could account for the physiological basis of low-level inflammation of depression.

          Limitations

          This is a cross-sectional study and the sample size is comparatively small. Though several diet-related factors were controlled in the study, there is no quantified assessment of it.

          Most cited references20

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          FLASH: fast length adjustment of short reads to improve genome assemblies.

          Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome. We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds. The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash. t.magoc@gmail.com.
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            Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression.

            Many studies have explored the association between soluble interleukin-2 receptor (sIL-2R), cytokines and major depressive disorder (MDD). However, the results of these studies were not consistent. The aim of our study is to compare the levels of sIL-2R and cytokines in the blood between MDD patients and controls by a meta-analysis and to identify moderators accounting for potential heterogeneity in the levels of sIL-2R and cytokines in MDD patients versus controls by meta-regression analyses. A comprehensive literature search was performed to identify studies comparing the levels of sIL-2R and cytokines between MDD patients and controls. We pooled the effect sizes for standardized mean differences (SMD) of the levels of sIL-2R and cytokines. We also performed meta-regression and sensitivity analyses to investigate the roles of age, gender, sample type, ethnic origin and selected studies' quality in explaining potential heterogeneity and differences in results respectively. Twenty-nine studies were selected for this analysis. The levels of sIL-2R, TNF-α and IL-6 in MDD patients were significantly higher than those of healthy controls (SMD=0.555, p<0.001, SMD=0.567, p=0.010; SMD=0.680, p<0.001). Mean age of all subjects was a significant moderator to explain the high heterogeneity of IL-6. Sensitivity analysis found that European but not non-European subjects have higher levels difference of sIL-2R, TNF-α and IL-1β between MDD patients and controls. The severity of MDD was not considered. The blood levels of sIL-2R, TNF-α and IL-6 were significantly higher in MDD patients than controls. Age, samples source and ethnic origins may play a potential role in heterogeneity. Copyright © 2011 Elsevier B.V. All rights reserved.
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              CSF Concentrations of Brain Tryptophan and Kynurenines during Immune Stimulation with IFN-alpha: Relationship to CNS Immune Responses and Depression

              Cytokine-induced activation of indoleamine 2,3 dioxygenase (IDO) catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA). QUIN and KA are neuroactive and may contribute to the behavioral changes experienced by some patients during exposure to inflammatory stimuli such as interferon (IFN)-alpha. A relationship between depressive symptoms and peripheral blood TRP, KYN and KA during IFN-alpha treatment has been described. However, whether peripheral blood changes in these IDO catabolites are manifest in the brain and whether they are related to central nervous system cytokine responses and/or behavior is unknown. Accordingly, TRP, KYN, QUIN and KA were measured in cerebrospinal fluid (CSF) and blood along with CSF concentrations of relevant cytokines, chemokines and soluble cytokine receptors in 27 patients with hepatitis C after ~12 weeks of either treatment with IFN-alpha (n=16) or no treatment (n=11). Depressive symptoms were assessed using the Montgomery Asberg Depression Rating Scale. IFN-alpha significantly increased peripheral blood KYN, which was accompanied by marked increases in CSF KYN. Increased CSF KYN was in turn associated with significant increases in CSF QUIN and KA. Despite significant decreases in peripheral blood TRP, IFN-alpha had no effect on CSF TRP concentrations. Increases in CSF KYN and QUIN were correlated with increased CSF IFN-alpha, soluble tumor necrosis factor-alpha receptor 2 (sTNFR2) and monocyte chemoattractant protein (MCP)-1 as well as increased depressive symptoms. In conclusion, peripheral administration of IFN-alpha activated IDO in concert with central cytokine responses, resulting in increased brain KYN, QUIN, KA, and ultimately depressive symptoms.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2018
                03 December 2018
                : 14
                : 3329-3337
                Affiliations
                [1 ]National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China, liangying1980@ 123456bjmu.edu.cn
                [2 ]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China, kangy@ 123456big.ac.cn
                [3 ]Department of Psychiatry, Beijing Hospital of Chinese Traditional and Western Medicine, Beijing, China
                [4 ]Beijing Gene Tangram Technology Co. Ltd, Beijing, China
                Author notes
                Correspondence: Ying Liang, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Institute of Mental Health, Ministry of Health, Peking University, No 51, Huayuanbei Rd, Haidian District, Beijing 100191, China, Tel/fax +86 108 280 1955, Email liangying1980@ 123456bjmu.edu.cn
                Yu Kang, Beijing Institute of Genomics, Chinese Academy of Sciences, No 1 Beichen West Rd, Chaoyang District, Beijing 100101, China, Tel +86 108 409 7546, Fax +86 108 409 7720, Email kangy@ 123456big.ac.cn
                [*]

                These authors contributed equally to this work

                Article
                ndt-14-3329
                10.2147/NDT.S188340
                6284853
                30584306
                4843e41b-8340-45f7-b895-2b04569a24ff
                © 2018 Huang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Clinical Trial Report

                Neurology
                gut microbiota,brain–gut axis,depression,firmicutes,short-chain fatty acids
                Neurology
                gut microbiota, brain–gut axis, depression, firmicutes, short-chain fatty acids

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