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      Gut microbial dysbiosis in individuals with Sjögren’s syndrome

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          Abstract

          Background

          Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined.

          Results

          Results showed that Firmicutes was the dominant phylum in the gut, comprising 40–60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p = 0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs.

          Conclusions

          In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.

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          Most cited references38

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          An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis

          Background The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been reported, though the specific components of the microbiota that affect the host response leading to disease remain unknown. However, there is limited information on the role of gut microbiota in RA. In this study we aimed to define a microbial and metabolite profile that could predict disease status. In addition, we aimed to generate a humanized model of arthritis to confirm the RA-associated microbe. Methods To identify an RA biomarker profile, the 16S ribosomal DNA of fecal samples from RA patients, first-degree relatives (to rule out environment/background as confounding factors), and random healthy non-RA controls were sequenced. Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link. The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis. Results Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels. A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria, with a decrease in abundant taxa in patients with RA compared with controls. Prediction models based on the random forests algorithm suggested that three genera, Collinsella, Eggerthella, and Faecalibacterium, segregated with RA. The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A. A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis. Conclusions These observations suggest dysbiosis in RA patients resulting from the abundance of certain rare bacterial lineages. A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0299-7) contains supplementary material, which is available to authorized users.
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            Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease.

            To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA).
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              Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007).

              (2007)
              The role of the Diagnostic Methodology Subcommittee of the Dry Eye Workshop was 1) to identify tests used to screen, diagnose and monitor dry eye disease, 2) to establish criteria for test performance, and 3) to consider the utility of tests in a variety of clinical settings. The committee created a database of tests used to diagnose and monitor dry eye, each compiled by an expert in the field (rapporteur) and presented within a standard template. Development of the templates involved an iterative process between the Chairman of the subcommittee, the rapporteurs, and, at times, an additional group of expert reviewers. This process is ongoing. Each rapporteur was instructed on how to the complete a template, using a proforma template and an example of a completed template. Rapporteurs used the literature and other available sources as the basis for constructing their assigned template. The chairman of the subcommittee modifed the template to produce a standardized version and reviewed it with the rapporteur. The completed database will be searchable by an alphabetical list of test names, as well as by functional groupings, for instance, tests of aqueous dynamics, lipid functions, etc. The templates can be accessed on the website of the Tear Film and Ocular Surface Society (www.tearfilm.org). This report provides a general overview of the criteria applied in the development of tests for screening and diagnosis.
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                Author and article information

                Contributors
                rxm1100@med.miami.edu
                awatane@med.miami.edu
                monika.farhangi@knights.ucf.edu
                kcavuoto@med.miami.edu
                tbleith@gmail.com
                shrish@openbiome.org
                agalor@med.miami.edu
                santanu.banerjee@med.miami.edu
                Journal
                Microb Cell Fact
                Microb. Cell Fact
                Microbial Cell Factories
                BioMed Central (London )
                1475-2859
                15 April 2020
                15 April 2020
                2020
                : 19
                : 90
                Affiliations
                [1 ]GRID grid.26790.3a, ISNI 0000 0004 1936 8606, Department of Surgery, , University of Miami, ; Miami, FL USA
                [2 ]GRID grid.26790.3a, ISNI 0000 0004 1936 8606, Bascom Palmer Eye Institute, , University of Miami, ; Miami, FL USA
                [3 ]GRID grid.484420.e, Miami Veterans Administration Medical Center, ; Miami, FL USA
                [4 ]GRID grid.489033.5, OpenBiome, ; Cambridge, MA USA
                Article
                1348
                10.1186/s12934-020-01348-7
                7158097
                32293464
                24d57c93-31d0-4c9a-8fdb-d42d68eaa062
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 January 2020
                : 5 April 2020
                Funding
                Funded by: National Institutes of Health (US)
                Award ID: P30EY014801
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000738, U.S. Department of Veterans Affairs;
                Award ID: EPID-006-15S
                Award ID: R01EY026174
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100014454, Leonard M. Miller School of Medicine, University of Miami;
                Award ID: Start-up Funds
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Biotechnology
                sjögren’s syndrome,dry eye,gut microbiome,dysbiosis
                Biotechnology
                sjögren’s syndrome, dry eye, gut microbiome, dysbiosis

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