The stool microbiome in patients with psoriatic arthritis is altered but, unlike the skin microbiome, does not change following treatment: evidence for an underlying inflammatory drive from the intestine

Abstract

AbstractObjectivesThere 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.MethodsWe 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.ResultsAs 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.ConclusionsThese 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.Key MessagesWhat is already known about this subject?Intestinal bacterial populations are altered in people with inflammatory diseases, including psoriatic arthritis (PsA).Interactions between bacteria and the immune system may contribute to the pathogenesis of inflammatory diseases.What does this study add?While skin bacteria in patients with PsA revert towards normal after treatment, stool bacteria remain different from healthy individuals.Specific bacterial types are correlated with specific changes in the immune system in PsA.How might this impact on clinical practice or future developments?Identification of the bacteria that drive persistent underlying changes in the immune response may enable these to be targeted.