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

We thank McGonagle et al 1 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 …