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.
Trial registration number NCT03058900.
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.
Trial registration number NCT03058900.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e003750 |
| Tidsskrift | RMD Open |
| Vol/bind | 10 |
| Udgave nummer | 1 |
| Antal sider | 13 |
| ISSN | 2056-5933 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Correction: 10.1136/rmdopen-2023-003750corr1Link: https://rmdopen.bmj.com/content/10/1/e003750corr1
Funding Information:
We thank all patients, FMT donors, and healthy controls fo their important contribution. This study was supported by Sygeforsikringen 'danmark' (2022-0026), Fabrikant Vilhelm Pedersen’s Mindelegat (on recommendation by the Novo Nordisk Foundation), Medicin Fund of the Danish Regions (Regionernes Medicin- og behandlingspulje), University of Southern Denmark Research Fund, the Danish Rheumatism Association, the Danish Psoriasis Research Foundation, and Research Fund of Odense University Hospital. JRM, BHM, and the Division of Digestive Diseases at Imperial College London receive financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002).
Funding Information:
This study was supported by Sygeforsikringen 'danmark' (2022-0026), Fabrikant Vilhelm Pedersen’s Mindelegat (on recommendation by the Novo Nordisk Foundation), Medicin Fund of the Danish Regions (Regionernes Medicin- og behandlingspulje), University of Southern Denmark Research Fund, the Danish Rheumatism Association, the Danish Psoriasis Research Foundation, and Research Fund of Odense University Hospital. JRM, BHM, and the Division of Digestive Diseases at Imperial College London receive financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002).
Publisher Copyright:
© Author(s) (or their employer(s)) 2024.