Objectives There is growing recognition that interactions between bacteria and the immune response may contribute to inflammation in psoriatic arthritis (PsA). To identify how the skin and stool microbiota may contribute to pathogenesis, we analysed the microbiota and immunophenotype of patients with PsA before and after therapy. Methods We examined the phenotype of PBMCs as well as skin and stool microbiota from 22 healthy volunteers, 7 PsA patients receiving methotrexate, and 23 PsA patients treated with biologic DMARDs. Samples for microbiome analysis were collected before therapy and after 3-6 months. First, we identified differences in the skin and stool microbiota between PsA patients and health volunteers. We then assessed changes in the microbiome occurring after treatment. Results. As hypothesised, treatment responses were reflected by changes in both the skin microbiota and in the immunophenotype. However, in the stool samples, dysbiosis persisted after therapy. This dysbiosis was associated with changes in the peripheral blood immunophenotype. Correlation analysis enabled identification not only of specific microbial taxa (Clostridial species) that contributed to the persistent dysbiosis, but also of interactions between taxa and the immune response. Conclusions These analyses indicate that specific Clostridial species contribute to persistent gut dysbiosis in PsA, and their prevalence is associated with specific immunological changes that are not altered by treatment. Thus, an underlying inflammatory response in the intestine appears to contribute to the pathogenesis of PsA.

Author SS reports institutional grant funding from Amgen (previously Celgene), Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen and UCB consultancy/speaker fees from AbbVie, Amgen, Eli Lilly, GSK, Janssen and UCB

This work was funded by Versus Arthritis Microbiome Pathfinder Award (grant ref 21130) and by NIHR Manchester Biomedical Research Centre

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of West of Scotland REC 4, 14/WS/1035, North West 13/NW0068 and MREC 99/8/84 gave ethical approcal for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors