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      Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model

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          Abstract

          Objective

          This study was to inspect the antidepressant‑like effect of prebiotics and probiotics, and to explore the effect of modulating gut microbiota on the serotonin (5‐HT) metabolism.

          Methods

          Fifty rats were separated into control and other four groups randomly. The four groups underwent the chronic unpredictable mild stress (CUMS) intervention with or without prebiotics and probiotics ( Bifidobacterium longum, L. rhamnosus) treatment. After weighted, the animals underwent a series of behavioral tests comprising the sucrose preference test (SPT) and the forced swimming test (FST). Central and colonic serotonin levels and relative metabolism factors were measured and analyzed. Microbiota was examined by 16S rRNA gene pyrosequencing.

          Results

          CUMS intervention caused a decrease in body weight, an increase in FST, and a decrease in SPT. Prebiotics and probiotics all ameliorated the CUMS‐induced loss of weight and depressive‐like behaviors to a certain extent, especially L. rhamnosus. Compared with the group of CUMS intervention, the rats of probiotics and probiotics treatment had a tendency to reduce colonic 5‐HT and increase 5‐HT in frontal cortex and hippocampus. However, there was no significant difference in peripheral blood 5‐HT among these groups. Furthermore, CUMS caused noteworthy gut microbiota variations at the phylum and other levels in rats. Remarkably, there were considerable relations of perturbed gut microbiota with the changed metabolism of 5‐HT.

          Conclusion

          In conclusion, these findings implied that prebiotics and probiotics have antidepressive effects, and a considerable effect on the regulation of 5‐HT metabolism, especially L. rhamnosus.

          Abstract

          We selected common prebiotics and probiotics to explore the effect of modulating gut microbiota on serotonin(5‐HT) metabolism. The results confirmed that prebiotics and probiotics could ameliorate depressive‐like behaviors and alleviate chronic unpredictable mild stress (CUMS) induced raised colonic 5‐HT and reduced central 5‐HT through the altered metabolic enzymes. Furthermore, CUMS caused noteworthy gut microbiota variations, and there were considerable relations of perturbed gut microbiota with the changed metabolism of 5‐HT.

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          Most cited references37

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          Responding to public and private politics: corporate disclosure of climate change strategies

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            The catecholamine hypothesis of affective disorders: a review of supporting evidence.

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              Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics.

              As a prevalent, life-threatening and highly recurrent psychiatric illness, depression is characterized by a wide range of pathological changes; however, its etiology remains incompletely understood. Accumulating evidence supports that gut microbiota affects not only gastrointestinal physiology but also central nervous system (CNS) function and behavior through the microbiota-gut-brain axis. To assess the impact of gut microbiota on fecal metabolic phenotype in depressive conditions, an integrated approach of 16S rRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in chronic variable stress (CVS)-induced depression rat model. Interestingly, depression led to significant gut microbiota changes, at the phylum and genus levels in rats treated with CVS compared to controls. The relative abundances of the bacterial genera Marvinbryantia, Corynebacterium, Psychrobacter, Christensenella, Lactobacillus, Peptostreptococcaceae incertae sedis, Anaerovorax, Clostridiales incertae sedis and Coprococcus were significantly decreased, whereas Candidatus Arthromitus and Oscillibacter were markedly increased in model rats compared with normal controls. Meanwhile, distinct changes in fecal metabolic phenotype of depressive rats were also found, including lower levels of amino acids, and fatty acids, and higher amounts of bile acids, hypoxanthine and stercobilins. Moreover, there were substantial associations of perturbed gut microbiota genera with the altered fecal metabolites, especially compounds involved in the metabolism of tryptophan and bile acids. These results showed that the gut microbiota was altered in association with fecal metabolism in depressive conditions. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be further applied to assess pathogenesis of depression.
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                Author and article information

                Contributors
                phdzdl@yahoo.com
                Journal
                Neurogastroenterol Motil
                Neurogastroenterol. Motil
                10.1111/(ISSN)1365-2982
                NMO
                Neurogastroenterology and Motility
                John Wiley and Sons Inc. (Hoboken )
                1350-1925
                1365-2982
                19 July 2019
                October 2019
                : 31
                : 10 ( doiID: 10.1111/nmo.v31.10 )
                : e13677
                Affiliations
                [ 1 ] School of Nursing Qingdao University Qingdao China
                [ 2 ] Department of Urology, Qingdao Municipal Hospital Qingdao University Qingdao China
                [ 3 ] Department of Anorectal Surgery Tongde hospital of Zhejiang Provence HangZhou China
                [ 4 ] Department of Ultrasound The Affiliated Hospital of Qingdao University Qingdao China
                [ 5 ] Center of Colon and Rectum, Qingdao Municipal Hospital Qingdao University Qingdao China
                Author notes
                [*] [* ] Correspondence

                Dianliang Zhang, Center of Colon and Rectum, Qingdao Municipal Hospital, Qingdao University, No. 1 Jiaozhou Road, Qingdao 266011, Shandong Province, China.

                Email: phdzdl@ 123456yahoo.com

                Author information
                https://orcid.org/0000-0002-4107-4351
                Article
                NMO13677
                10.1111/nmo.13677
                6852474
                31323174
                e6840c6a-a387-425d-9915-f4777ed07443
                © 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 17 April 2019
                : 19 June 2019
                : 01 July 2019
                Page count
                Figures: 7, Tables: 3, Pages: 13, Words: 8298
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81270448
                Award ID: 81470890
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                October 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.1 mode:remove_FC converted:13.11.2019

                Gastroenterology & Hepatology
                depression,gut microbiota,gut‐brain axis,prebiotics,probiotics,serotonin

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