POS1028 Long-term response to faecal microbiota transplantation in psoriatic arthritis is associated with gut microbiota community types in recipients

Background: An abnormal composition of gut bacteria in combination with alterations of microbiota-derived metabolites may be important environmental factors contributing to the natural history of disease and may potentially affect drug responses in immune-mediated conditions. Hence, modulation of the intestinal microbiota is increasingly being highlighted as a potential novel complementary therapy to immunomodulatory drugs. Faecal microbiota transplant (FMT) products contain minimally manipulated microbial communities donated by healthy, thoroughly-screened individuals. In a previous randomised trial (FLORA) investigating safety and efficacy of one FMT in methotrexate (MTX)-treated patients with severe psoriatic arthritis (PsA), we observed transitory beneficial clinical effects within weeks of the intervention, while sustained, long-term effects was only observed in 40% treated [1]. Investigations into biological mechanisms that can explain the observed differences in treatment outcome following FMT in immune-mediated arthritis have not previously been reported. Objectives: We therefore conducted a shotgun metagenomics study to explore how gut bacterial signatures in patients and engraftment of specific strains associated with long-term response to FMT in active PsA. Methods: This exploratory study is based on the FLORA trial cohort encompassing 31 patients with moderate-to-high PsA disease activity and 4 FMT donors. Out of fifteen patients receiving one single-donor FMT (the intention-to-treat population, ITT), thirteen were included in the per-protocol (PP) population. The reasons for excluding two patients from the PP population included major changes in living environment and not receiving the full dose of the FMT product. Stool samples were collected before and after FMT (week 4, 12, and 26). We performed shotgun metagenomics to characterise the gut microbiota features. Results: At baseline, 17 PsA patients (55%) had a gut microbiota community (GMC) type dominated by the Bacteroides genus (B-type) while 14 (45%) had a Prevotella -driven community type (P-type). The B- and P-type patients did not differ in disease activity nor demographics at baseline (Table 1), but B-type patients had a significantly higher species diversity compared to P-type patients (p=0.005). In the PP population, five out of seven B-type patients vs none out of six P-type patients (p=0.021) achieved a long-term clinical beneficial response at week 26. Although this difference was not statistically significant in the ITT population (5 vs 1, p=0.12), the remission rate in B-type patients was still four times higher compared to P-type patients. In B-type patients, strain richness significantly increased from baseline to week 4 (p=0.016) and week 26 (p=0.016) (Figure 1A). In contrast, alpha diversity only showed an increasing trend (p=0.062) at week 4 in P-type patients, and this trend was only temporary, as both alpha diversity (p=0.062) and strain richness (p=0.062) showed a decreasing trend by week 12 (Figure 1A). Eighteen engrafted bacterial strains persisted only in B-type recipients by week 26 (Figure 1B), including a Bacteroides clarus strain, which demonstrated a negative effect size regarding arthritis pain and the physician's global assessment of disease. Table 1. Baseline demographics and disease characteristics of the B and P-type patients. Data are mean (SD) or n (%) unless otherwise stated. a Time since diagnosis of psoriatic arthritis is presented as median and interquartile range (IQR). HAQ-DI, Health Assessment Questionnaire Disability Index. SPARCC, Spondyloarthritis Research Consortium of Canada. DMARD, disease‑modifying anti-rheumatic drug. Figure 1Gut microbiota modifications following one faecal microbiota transplantation (FMT) in B- and P-type patients. B denotes patients with a gut microbiota community (GMC) type dominated by the Bacteroides genus (B-type) at baseline while P denote patients with a Prevotella -driven GMC (P-type). (A) Changes in strain richness and alpha diversity. P values were calculated using paired Wilcox test. (B) Long-term multi-recipient colonization (LMC) strains, defined as strains that engrafted and colonised in at least three patients by week 26. Eighteen LMC strains, which exclusively engrafted in B-type recipients at week 26, are marked with a star and a letter. The colour of the star distinguishes whether the strain colonized short-term in P-type recipients at week 4: purple indicates no colonization at week 4, while pink indicates colonization at week 4. SCFA, short-chain fatty acid Conclusion: This study shows for the first time that a Bacteroides -predominant GMC type (B-type) associates with long-term beneficial response following one FMT in patients with PsA. In contrast to patients having a Prevotella -dominated community type (P-type), strain richness significantly increased in B-type patients, including long-term engraftment of donor-specific bacterial strains. More research is encouraged to evaluate the clinical value of using GMC typing and other gut microbial features in guiding the selection of therapies and enhancing personalised treatment responses in relation to both the application of microbiota-targeted therapies such as FMT and the use of established disease-modifying anti-rheumatic drugs. REFERENCES: [1] Kragsnaes MS, Kjeldsen J, Horn HC, et al . Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial. Ann Rheum Dis 2021;80:1158-67. Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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