Fecal microbiota transplantation affects several inflammation-associated plasma proteins in psoriatic arthritis, suggesting systemic immune response induction, according to a recent exploratory study.
Psoriatic arthritis (PsA) is an immune-mediated disease associated with alterations in the gut microbial environment. As the gut microbiota can mediate inflammatory responses, one potential intervention for PsA is fecal microbiota transplantation (FMT). FMT involves the introduction of stool from a healthy donor into the patient’s gastrointestinal tract to modify their intestinal environment.
An analysis of data from the FLORA trial, a double-blind, randomized, sham-controlled trial, investigated the impact of FMT on 92 inflammation-associated plasma proteins in PsA patients. The study’s results are published in RMD Open.
Study Population
A total of 31 Danish patients with moderate-to-high peripheral PsA disease activity despite methotrexate treatment were enrolled in the randomized controlled trial. They were allocated to receive either gastroscopic-guided FMT (n=15) or sham transplantation (n=16). The mean patient age was 50.7 years, with 65% females. The study also comprised 31 age- and sex-matched healthy controls (HCs).
Inflammation-Associated Plasma Protein Levels Differ Significantly Between PsA and HCs
Hierarchical clustering to compare baseline protein profiles of the FMT and sham PsA groups and the two control groups (HCs and donors) revealed that the majority of the study population was separated into two clusters, one comprising mostly patients (22 out of 31) and one comprising mostly HCs (27 out of 35). Of the four donors, two were located in the HC-dominated cluster and two in the patient-dominated cluster. There were significant differences in the levels of 26 proteins between PsA patients and HCs.
FMT Affects the Levels of Several Inflammation-Associated Plasma Proteins
The FMT group demonstrated significant changes in the levels of 12 inflammation-associated plasma proteins across all time points (baseline, week 4, week 12, and week 26). Of these 12, 11 showed an overall increase: tumor necrosis factor (TNF) (p<0.001), TNF superfamily member 12 (p=0.003), cub domain-containing protein 1 (CDCP1) (p=0.003), interferon-γ (IFN-γ) (p=0.004), T-cell surface glycoprotein CD8 alpha chain (p=0.012), T-cell surface glycoprotein CD5 (p=0.018), CC motif chemokine 25 (CCL-25) (p=0.044), FMS-related tyrosine kinase 3 ligand (p=0.044), fibroblast growth factor 23 (FGF-23) (p=0.045), T-cell surface glycoprotein CD6 (p=0.049), and signaling lymphocytic activation molecule (SLAMF1) (p=0.011). Only caspase-8 demonstrated sustained reduced levels post-FMT (p=0.045).
The sham group demonstrated significant changes in the levels of six proteins, all showing an initial decrease from baseline to week 12, followed by an increase from week 12 to week 26: stem cell factor (SCF) (p=0.006), CCL-3 (p=0.012), CCL-25 (p=0.018), interleukin-5 (IL-5) (p=0.022), monocyte chemotactic protein 4 (MCP-4) (p=0.029), and C-X-C motif chemokine 5 (CXCL-5) (p=0.043).
Protein Differences and Immune Responses in FMT for Psoriatic Arthritis
Five proteins differed significantly between FMT and sham-treated groups: TNF (p=0.002), IFN-γ (p=0.011), SCF (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). To explore whether some of the FMT group effects could be explained by treatment with TNF inhibitors, the top five proteins with the largest increase or decrease in normalized protein expression (NPX) value post-FMT were identified.
Confirming the mixed ANOVA results, FMT had the largest positive effect on IFN-γ, with sustained elevated levels, followed by Axin-1 and CCL-25. The largest negative effect was observed in CCL-19 and IL-6. Hence, FMT likely induces systemic immune responses in PsA. Comparing patients’ protein profiles to their respective donors’ on heatmap revealed no major systemic immunological donor-specific effects 4 weeks post-FMT.
Protein Levels Not Associated With Disease Activity in SpA
Analysis of the relations between baseline protein levels and four clinical disease activity measures (swollen joint count, Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis count, tender point count, and Health Assessment Questionnaire Disability Index (HAQ-DI)) revealed no significant relationship.
Source:
Kragsnæs, M. S., Jensen, J. R. B., Nilsson, A. C., Malik, M. A., Munk, H. L., Pedersen, J. B., Horn, H., Kruhøffer, M., Kristiansen, K., Mullish, B. H., Marchesi, J. R., Kjeldsen, J., Röttger, R., & Ellingsen, T. (2024). Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial. RMD Open, 10(1), e003750. https://doi.org/10.1136/rmdopen-2023-003750
