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      Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia

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          Abstract

          The gut microbiota plays important roles in the development of the host immune system. We have previously shown that a combination of 46 strains of commensal Clostridia isolated from conventionally reared mice can induce the accumulation of CD4 +Foxp3 + regulatory T (Treg) cells in the mouse colonic lamina propria. Subsequently, we succeeded in isolating and selecting 17 strains of Clostridia from a healthy human fecal sample that can significantly increase the number and function of colonic Treg cells in colonized rodents, thereby attenuating symptoms of experimental allergic diarrhea and colitis. Here we characterize each of the 17 strains of human-derived Clostridia in terms of sensitivity to antibiotics and ability to produce short chain fatty acids and other metabolites, and discuss their potential as biotherapeutics to correct dysbiosis and treat immune-inflammatory diseases.

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          Most cited references10

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          Intestinal commensal microbes as immune modulators.

          Commensal bacteria are necessary for the development and maintenance of a healthy immune system. Harnessing the ability of microbiota to affect host immunity is considered an important therapeutic strategy for many mucosal and nonmucosal immune-related conditions, such as inflammatory bowel diseases (IBDs), celiac disease, metabolic syndrome, diabetes, and microbial infections. In addition to well-established immunostimulatory effects of the microbiota, the presence of individual mutualistic commensal bacteria with immunomodulatory effects has been described. These organisms are permanent members of the commensal microbiota and affect host immune homeostasis in specific ways. Identification of individual examples of such immunomodulatory commensals and understanding their mechanisms of interaction with the host will be invaluable in designing therapeutic strategies to reverse intestinal dysbiosis and recover immunological homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Commensal Bacteria-Dependent Indole Production Enhances Epithelial Barrier Function in the Colon

            Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule mediating intercellular signals in bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF) mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo.
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              Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway.

              Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a pathway mediating hypoxia-induced cerebral vasodilation in studies monitoring vascular disposition in cerebellar slices and in intact mouse brains using two-photon intravital laser scanning microscopy. In this cascade, hypoxia elicits cerebral vasodilation via the coordinate actions of H(2)S formed by cystathionine β-synthase (CBS) and CO generated by heme oxygenase (HO)-2. Hypoxia diminishes CO generation by HO-2, an oxygen sensor. The constitutive CO physiologically inhibits CBS, and hypoxia leads to increased levels of H(2)S that mediate the vasodilation of precapillary arterioles. Mice with targeted deletion of HO-2 or CBS display impaired vascular responses to hypoxia. Thus, in intact adult brain cerebral cortex of HO-2-null mice, imaging mass spectrometry reveals an impaired ability to maintain ATP levels on hypoxia.
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                Author and article information

                Journal
                Gut Microbes
                Gut Microbes
                GMIC
                Gut Microbes
                Landes Bioscience
                1949-0976
                1949-0984
                01 May 2014
                18 March 2014
                01 May 2015
                : 5
                : 3
                : 333-339
                Affiliations
                [1 ]RIKEN Center for Integrative Medical Sciences (IMS-RCAI); Yokohama, Japan
                [2 ]Department of Biochemistry; School of Medicine; Keio University; Tokyo, Japan
                [3 ]Japan Science and Technology Agency; Precursory Research for Embryonic Science and Technology (PRESTO); Kawaguchi, Japan
                [4 ]Graduate School of Frontier Sciences; The University of Tokyo; Kashiwa, Japan
                [5 ]Japan Science and Technology Agency; Core Research for Evolutional Science and Technology (CREST); Kawaguchi, Japan
                [6 ]Japan Science and Technology Agency; Exploratory Research for Advanced Technology (ERATO); Suematsu Gas Biology Project; Tokyo, Japan
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Correspondence to: Kenya Honda, Email: kenya@ 123456rcai.riken.jp
                Article
                2013GUTMICROBES0086 28572
                10.4161/gmic.28572
                4153770
                24642476
                96be61e0-0fa4-4340-a83e-4163c86c1500
                Copyright © 2014 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 28 January 2014
                : 17 March 2014
                Categories
                Article Addendum

                Microbiology & Virology
                clostridia,treg,gut microbiota
                Microbiology & Virology
                clostridia, treg, gut microbiota

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