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Response to: ‘Correspondence on ‘Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial’’ by McGonagle et al
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  1. Maja Skov Kragsnaes1,2,
  2. Jens Kjeldsen2,3,
  3. Hans Christian Horn1,
  4. Heidi Lausten Munk1,
  5. Jens Kristian Pedersen4,
  6. Søren Andreas Just4,
  7. Palle Ahlquist5,
  8. Jesper Rømhild Davidsen2,6,
  9. Anna Christine Nilsson7,
  10. Richard Röttger8,
  11. Mogens Kruhøffer9,
  12. Julian R Marchesi10,
  13. Karsten Kristiansen11,12,
  14. Robin Christensen2,13,
  15. Torkell Ellingsen1,2
  1. 1Rheumatology Research Unit, Department of Rheumatology, Odense University Hospital, Odense, Denmark
  2. 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  3. 3Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark
  4. 4Section of Rheumatology, Department of Medicine, Svendborg Hospital, Svendborg, Denmark
  5. 5Reumaklinik Fyn, Odense, Denmark
  6. 6South Danish Center for Interstitial Lung Diseases, Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark
  7. 7Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
  8. 8Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, Denmark
  9. 9BioXpedia, Aarhus, Denmark
  10. 10Division of Digestive Diseases, Imperial College London Faculty of Medicine, London, UK
  11. 11Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
  12. 12Institute of Metagenomics, BGI-Shenzhen, Shenzhen, China
  13. 13Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
  1. Correspondence to Professor Torkell Ellingsen, Rheumatology Research Unit, Department of Rheumatology, Odense University Hospital, 5000 Odense, Denmark; torkell.ellingsen{at}rsyd.dk

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We thank McGonagle et al1 for their insightful comments on our manuscript on faecal microbiota transplantation (FMT) in active peripheral psoriatic arthritis (PsA), known as the FLORA trial.2 We agree that the clinical findings of this first double-blind, randomised, trial of FMT in immune-mediated arthritis warrant further investigation into the underlying biological mechanisms coupling gut composition, the intestinal barrier–microbiotal interaction, and systemic inflammation in PsA and related chronic inflammatory diseases. Indeed, evidence linking the composition of the gut microbiota and initiation/progression of immune-mediated disease is limited and is primarily derived from animal models.3 Suggested mechanisms encompass failure to induce immunological tolerance,4 which may direct the T cell repertoire towards a pro-inflammatory phenotype including Th17 differentiation and activation seen in PsA, loss of epithelial integrity5 and systemic translocation due to local inflammation and/or tissue damage that may enable trafficking of both activated immune cells and antigenic material to distant sites thereby creating perpetual systemic inflammatory stimuli6 by epitope spreading,7 bystander activation8 and/or molecular mimicry.9 …

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