Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial

Maja Skov Kragsnaes*, Jennifer Rugaard Bregndahl Jensen, Anna Christine Nilsson, Muhammad Irfan Malik, Heidi Lausten Munk, Jens Kristian Pedersen, Hans Christian Horn, Mogens Kruhøffer, Karsten Kristiansen, Benjamin H. Mullish, Julian R. Marchesi, Jens Kjeldsen, Richard Röttger, Torkell Ellingsen

*Corresponding author for this work

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Abstract

Objectives The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins. Methods This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel). Results Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6. Conclusions Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ.

Original languageEnglish
Article numbere003750
JournalRMD Open
Volume10
Issue number1
ISSN2056-5933
DOIs
Publication statusPublished - 30. Jan 2024

Keywords

  • Antigens, Neoplasm
  • Arthritis, Psoriatic/therapy
  • Cell Adhesion Molecules
  • Fecal Microbiota Transplantation/adverse effects
  • Humans
  • Inflammation/etiology
  • Interleukin-6
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha

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