{
  "abstract": "Introduction An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.Methods and analysis This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.Ethics and dissemination No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.PROSPERO registration number CRD42025644244.",
  "authors": [
    {
      "affiliations": [
        "OUH Frontline Centre for Applied Microbiota and Mucosal Barrier Research (MICARE), Odense University Hospital, Odense, Denmark",
        "Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark"
      ],
      "name": "Maja Skov Kragsnaes"
    },
    {
      "affiliations": [
        "Division of Rheumatology, HUG, Geneva, Switzerland"
      ],
      "name": "Benoit Thomas P Gilbert"
    },
    {
      "affiliations": [
        "Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark",
        "Department of Rheumatology, Odense University Hospital, Odense, Denmark"
      ],
      "name": "Bjørk Khaliqi Sofíudóttir"
    },
    {
      "affiliations": [
        "Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK",
        "Leeds Institute of Medical Research, University of Leeds, Yorkshire, UK"
      ],
      "name": "Christopher Michael Rooney"
    },
    {
      "affiliations": [
        "Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark"
      ],
      "name": "Sebrina Maj-Britt Hansen"
    },
    {
      "affiliations": [
        "Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy"
      ],
      "name": "Daniele Mauro"
    },
    {
      "affiliations": [
        "Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK",
        "St Mary’s Hospital, Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK"
      ],
      "name": "Benjamin H Mullish"
    },
    {
      "affiliations": [
        "Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia"
      ],
      "name": "Anne-Sophie Bergot"
    },
    {
      "affiliations": [
        "Leeds Institute of Rheumatic and Musculoskeletal Medicine, NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK"
      ],
      "name": "Kulveer Singh Mankia"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA"
      ],
      "name": "Niti Goel"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway"
      ],
      "name": "Gunnstein Bakland"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University Hospital of North Norway, Harstad, Norway"
      ],
      "name": "Peter Holger Johnsen"
    },
    {
      "affiliations": [
        "Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK"
      ],
      "name": "Jesus Miguens Blanco"
    },
    {
      "affiliations": [
        "Microbiome Systems research group at the Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "Simone Li"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Ghent, Ghent, Belgium",
        "Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Flanders Institute for Biotechnology, Ghent, Belgium"
      ],
      "name": "Emilie Dumas"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Esbjerg and Grindsted Hospital, Esbjerg, Denmark"
      ],
      "name": "Philip Rask Lage-Hansen"
    },
    {
      "affiliations": [
        "Amsterdam UMC, Amsterdam Rheumatology & Immunology Center, University of Amsterdam, Amsterdam, Netherlands"
      ],
      "name": "Carlijn Wagenaar"
    },
    {
      "affiliations": [
        "Microbiotica, Chesterford Research Park, Little Chesterford, UK"
      ],
      "name": "Ghaith Bakdash"
    },
    {
      "affiliations": [
        "Microbiotica, Chesterford Research Park, Little Chesterford, UK"
      ],
      "name": "Mat Robinson"
    },
    {
      "affiliations": [
        "Laboratory of Integrative Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Karsten Kristiansen"
    },
    {
      "affiliations": [
        "Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK"
      ],
      "name": "Julian R Marchesi"
    },
    {
      "affiliations": [
        "Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Department of Internal Medicine 3, Universitätsklinikum Erlangen, Erlangen, Germany"
      ],
      "name": "Georg Schett"
    },
    {
      "affiliations": [
        "Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany",
        "Department of Internal Medicine 3, Universitätsklinikum Erlangen, Erlangen, Germany"
      ],
      "name": "Mario M Zaiss"
    },
    {
      "affiliations": [
        "Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, UK"
      ],
      "name": "Mine Orlu"
    },
    {
      "affiliations": [
        "Amsterdam UMC, Amsterdam Rheumatology & Immunology Center, University of Amsterdam, Amsterdam, Netherlands"
      ],
      "name": "Dirkjan van Schaadenburg"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Rheumatology, New York University Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Jose U Scher"
    },
    {
      "affiliations": [
        "The Leeds Institute for Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"
      ],
      "name": "Dennis McGonagle"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University Hospital Ghent, Ghent, Belgium",
        "Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Flanders Institute for Biotechnology, Ghent, Belgium"
      ],
      "name": "Dirk Elewaut"
    },
    {
      "affiliations": [
        "Service de rhumatologie, Hôpital Ambroise Paré, Neuilly-sur-Seine, Île-de-France, France",
        "Université de Versailles St Quentin en Yvelines, Inserm, Infection et Inflammation, Université Paris-Saclay, Montigny le Btx, Île-de-France, France"
      ],
      "name": "Maxime Breban"
    },
    {
      "affiliations": [
        "Department of Medicine, School of Epidemiology and Public Health, Bruyere Research Institute, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada"
      ],
      "name": "Peter Tugwell"
    },
    {
      "affiliations": [
        "Division of Rheumatology, HUG, Geneva, Switzerland"
      ],
      "name": "Axel Finckh"
    },
    {
      "affiliations": [
        "Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy"
      ],
      "name": "Francesco Ciccia"
    },
    {
      "affiliations": [
        "Institute of Musculoskeletal Medicine, Department of Translational Rheumatology and Immunology, University of Münster, Münster, Germany",
        "Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA",
        "Department of Internal Medicine, Section of Rheumatology and Clinical Immunology, University Hospital Münster, Münster, Germany"
      ],
      "name": "Martin A Kriegel"
    },
    {
      "affiliations": [
        "Department of Rheumatology, CHU de Montpellier, Montpellier, France"
      ],
      "name": "Claire Daien"
    },
    {
      "affiliations": [
        "OUH Frontline Centre for Applied Microbiota and Mucosal Barrier Research (MICARE), Odense University Hospital, Odense, Denmark",
        "Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark"
      ],
      "name": "Torkell Ellingsen"
    },
    {
      "affiliations": [
        "Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark",
        "the Parker Institute, Section for Biostatistics and Evidence-Based Research, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark"
      ],
      "name": "Robin Christensen"
    },
    {
      "affiliations": [],
      "name": "EULAR Study Group MICMUC"
    }
  ],
  "title": "Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials",
  "uid": "8b6605b3-b22a-53a4-b524-398e3547d7c7"
}