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30 Department of Medicine, School of Epidemiology and Public Health, Bruyere Research Institute, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada 31 Institute of Musculoskeletal Medicine, Department of Translational Rheumatology and Immunology, University of Münster, Münster, Germany 32 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA 33 Department of Internal Medicine, Section of Rheumatology and Clinical Immunology, University Hospital Münster, Münster, Germany 34 Department of Rheumatology, CHU de Montpellier, Montpellier, France 35 the Parker Institute, Section for Biostatistics and Evidence-Based Research, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark Acknowledgements We are very grateful to our MICMUC collaborators Alf Kastbom, Valeria Rios Rodriguez, Giuliana Guggino and Sara Susanne Raanes for their valuable academic input and constructive feedback during the final revision of this manuscript. Collaborators EULAR Study Group MICMUC: Maja Skov Kragsnaes, Benoît Thomas P. Gilbert, Christopher Michael Rooney, Daniele Mauro, Benjamin H. Mullish, Anne- Sophie Bergot, Kulveer Singh Mankia, Niti Goel, Gunnstein Bakland, Peter Holger Johnsen, Sara Susanne Raanes, Jesus Miguens Blanco, Simone Li, Emilie Dumas, Carlijn Wagenaar, Alf Kastbom, Valeria Rios Rodriguez, Giuliana Guggino, Ghaith Bakdash, Mat Robinson, Karsten Kristiansen, Julian R. Marchesi, Georg Schett, Mario M. Zaiss, Dennis McGonagle, Dirkjan van Schaadenburg, Jose U. Scher, Dirk Elewaut, Maxime Breban, Axel Finckh, Francesco Ciccia, Martin A. Kriegel, Claire Daien, Torkell Ellingsen. Contributors MSK, TE and RC conceived the study. MSK drafted this protocol, which was critically revised by TE, RC, CD, BTPG, AF, MAK, DM, A-B, BHM, BKS, NG, PRL-H, MO, MB and JRM. All authors revised the protocol draft and contributed to the development of the selection criteria, the risk of bias assessment strategy and data extraction criteria. Members of the EULAR study group MICMUC provided expertise on microbiota and mucosal barrier research and microbiota-targeted therapies in IBD and AIRDs. RC provided statistical expertise. BKS developed the search strategy with input from the information scientist SM-BH, MSK, CMR and BHM. BTPG designed the REDCap database with input from MSK, CMR and BKS. All authors have read, provided feedback and approved the final manuscript. TE is the guarantor of this study. Funding This study is funded by Sygeforsikringen ‘danmark’ (2022-0026) and the Region of Southern Denmark Research Fund, and indirectly funded (through coverage of scientific staff salary) by Odense Universitetshospital, Syddansk Universitet, and Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, which is supported by a core grant from the Oak 23 Foundation (OCAY-18-774-OFIL). MAK is supported by a Global Team Science Award of the Lupus Research Alliance. The Division of Digestive Diseases receives financial support from the National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC) based at Imperial College London and Imperial College Healthcare NHS Trust. BHM is the recipient of ana UK Research and Innovation Medical Research Council grant (Clinician Scientist Fellowship, grant number: MR/Z504002/1). None of the funders have any role or influence on the paper. Competing interests MAK received consulting fees, honouraria, or research funds from Eligo Biosciences, Enterome, Novartis, Roche, Genentech, Bristol-Myers Squibb, AbbVie, Sanofi, and holds a patent on the use of microbiota manipulations to treat immune-mediated diseases (US Patent No. 11,058,756 B2). RC reports providing consulting on biostatistical matters, including trial design and statistical inference, for ZPD A/S (ScanDroitin), Image Analysis (trading as IAG, Image Analysis Group, UK), Compass Communications and Ascendis Pharma A/S, with payments made directly to him as an individual. He serves as Statistical Editor for Osteoarthritis and Cartilage and Acta Orthopaedica, with payments made directly to him. He is a founding member of the OMERACT Technical Advisory Group, a member of the GRADE Working Group, serves on the Statistical Advisory Board for BMJ Open, and is on the editorial boards of Arthritis Care & Research and Arthritis Research & Therapy. He is also an editor for the Cochrane Collaboration. The other authors have no competing interests. Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details. Patient consent for publication Not applicable.
We acknowledge that some of the trials that will be included in this review have been conducted before the widespread adoption of these outcome sets, which may limit the amount of accessible data that can be retrieved for one or more of these selected domains. However, all results will be interpreted carefully, taking this as well as other limitations into account. In conclusion, this systematic review and meta-analysis aims to provide a robust and comprehensive synthesis of current evidence regarding the efficacy and safety of microbiota-targeted therapies in AIRDs. The results will support the development of evidence-based clinical recommendations and inform future research directions in this emerging area. Author affiliations 1 OUH Frontline Centre for Applied Microbiota and Mucosal Barrier Research (MICARE), Odense University Hospital, Odense, Denmark 2 Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark 3 Division of Rheumatology, HUG, Geneva, Switzerland 4 Department of Rheumatology, Odense University Hospital, Odense, Denmark 5 Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK 6 Leeds Institute of Medical Research, University of Leeds, Yorkshire, UK 7 Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark 8 Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy 9 Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Imperial College London, London, UK 10 St Mary’s Hospital, Department of Gastroenterology and Hepatology, Imperial College Healthcare NHS Trust, London, UK 11 Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia 12 Leeds Institute of Rheumatic and Musculoskeletal Medicine, NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK 13 Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA 14 Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway 15 Department of Internal Medicine, University Hospital of North Norway, Harstad, Norway 16 Microbiome Systems research group at the Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia 17 Department of Rheumatology, University Hospital Ghent, Ghent, Belgium 18 Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Flanders Institute for Biotechnology, Ghent, Belgium 19 Department of Rheumatology, Esbjerg and Grindsted Hospital, Esbjerg, Denmark 20 Amsterdam UMC, Amsterdam Rheumatology & Immunology Center, University of Amsterdam, Amsterdam, Netherlands 21 Microbiotica, Chesterford Research Park, Little Chesterford, UK 22 Laboratory of Integrative Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark 23 Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany 24 Department of Internal Medicine 3, Universitätsklinikum Erlangen, Erlangen, Germany 25 Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, UK 26 Department of Medicine, Division of Rheumatology, New York University Grossman School of Medicine, New York, New York, USA 27 The Leeds Institute for Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK 28 Service de rhumatologie, Hôpital Ambroise Paré, Neuilly-sur-Seine, Île-de-France, France 29 Université de Versailles St Quentin en Yvelines, Inserm, Infection et Inflammation, Université Paris-Saclay, Montigny le Btx, Île-de-France, France
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Kragsnaes MS, et al . BMJ Open 2025; 15 :e101593. doi:10.1136/bmjopen-2025-101593
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