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      Gut Microbiota Dysbiosis Is Not Independently Associated With Neurocognitive Impairment in People Living With HIV

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          Abstract

          Gut microbiota dysbiosis, which has been linked to many neurological diseases, is common in HIV infection. However, its role in the pathogenesis of neurocognitive impairment is still not established. In this study, a total of 85 HIV infected subjects, naïve to antiretroviral therapy, were classified into two groups—those with HIV-associated neurological diseases (HAND) and those without, using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected from all subjects and microbiota were analyzed by 16S rRNA amplicon sequencing. Subjects with HAND were older ( P < 0.001), with lower levels of education ( P = 0.002), lower CD4 T-cell counts ( P = 0.032), and greater heterosexual preference ( P < 0.001), than those without HAND. Gut microbiota from subjects with HAND showed significantly lower α-diversity compared to gut microbiota from subjects without HAND (Shannon index, P = 0.003). To exclude confounding bias, 25 subjects from each group, with comparable age, gender, CD4 T-cell count, educational level and sexual preference were further analyzed. The two groups showed comparable α-diversity (for SOB index, Shannon index, Simpson index, ACE index, and Chao index, all with P-value > 0.05) and β-diversity (ANOSIM statistic = 0.010, P = 0.231). There were no significant differences in microbiota composition between the two groups after the correction for a false discovery rate. Consistently, microbiota from the two groups presented similar predictive functional profiles. Gut microbiota dysbiosis is not independently associated with neurocognitive impairment in people living with HIV.

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          Most cited references51

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          An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia

          HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T cell activation, inflammation and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1 infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared to uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1 infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation and blood T cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.
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            Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection.

            Despite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation.
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              Kynurenines in the CNS: recent advances and new questions.

              Various pathologies of the central nervous system (CNS) are accompanied by alterations in tryptophan metabolism. The main metabolic route of tryptophan degradation is the kynurenine pathway; its metabolites are responsible for a broad spectrum of effects, including the endogenous regulation of neuronal excitability and the initiation of immune tolerance. This Review highlights the involvement of the kynurenine system in the pathology of neurodegenerative disorders, pain syndromes and autoimmune diseases through a detailed discussion of its potential implications in Huntington's disease, migraine and multiple sclerosis. The most effective preclinical drug candidates are discussed and attention is paid to currently under-investigated roles of the kynurenine pathway in the CNS, where modulation of kynurenine metabolism might be of therapeutic value.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                28 January 2019
                2018
                : 9
                : 3352
                Affiliations
                [1] 1Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University , Shanghai, China
                [2] 2Department of Infectious Disease, Huashan Hospital, Fudan University , Shanghai, China
                [3] 3Department of Internal Medicine, Shanghai Medical College, Fudan University , Shanghai, China
                Author notes

                Edited by: Dimitris G. Hatzinikolaou, National and Kapodistrian University of Athens, Greece

                Reviewed by: Maria Jose Gosalbes, Centre for Biomedical Network Research (CIBER), Spain; John Zaunders, St Vincent’s Hospital Sydney, Australia

                *Correspondence: Jun Chen, qtchenjun@ 123456163.com Hongzhou Lu, luhongzhou@ 123456fudan.edu.cn

                Co-first authors

                This article was submitted to Systems Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2018.03352
                6362426
                30761121
                344526ac-d4dd-41dc-a20c-7b7f7cf98d6c
                Copyright © 2019 Zhang, Yang, Ji, Sun, Shen, Sun, Wang, Liu, Shen, Zhang, Chen and Lu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 October 2018
                : 31 December 2018
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 74, Pages: 10, Words: 0
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Foundation of Shanghai Municipal Commission of Health and Family Planning 10.13039/501100010032
                Funded by: Science and Technology Commission of Shanghai Municipality 10.13039/501100003399
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                hiv,cognitive,hiv-associated neurocognitive disorder,gut microbiota,predictive function

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