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In patients with active peripheral psoriatic arthritis, regardless of treatment outcome, fecal microbiota transplantation results in sustained elevation of IFN-γ levels, indicating a lasting immunomodulatory effect.
In a recent exploratory study, active psoriatic arthritis (PsA) patients possessed a unique immunological plasma protein profile when compared to healthy controls prior to fecal microbiota transplantation (FMT). FMT impacted various disease markers, notably sustaining elevated levels of interferon-alpha (IFN-γ), indicating its potential role in modulating the immune response in PsA.
In this pioneering effort to understand the intricate relationship between gut microbiota and inflammation, researchers conducted a study investigating the effects of FMT on 92 inflammation-linked plasma proteins in PsA-affected people. The findings, unveiled through the FLORA trial cohort, shed light on the potential of FMT for PsA. This study, led by a team of experts, encompassed 31 patients struggling with moderate-to-high peripheral PsA illness activity, despite conventional Methotrexate therapy.
The enrolled subjects underwent a 26-week, double-blind, randomized, sham-controlled trial, where they were allocated to get either a gastroscopic-guided healthy donor FMT (n=15) or a sham (n=16) procedure. Plasma samples from patients were collected at baseline, week 4, 12, and 26, while those from 31 age- and sex-matched healthy controls were collected only at baseline. Analysis was conducted using proximity extension assay technology.
The levels of 26 proteins illustrated significant disparities between PsA and healthy controls prior to FMT, with ten proteins notably elevated in PsA, including interleukin-6 (IL-6), C-C motif chemokine 20 (CCL20), C-C motif ligand 19 (CCL19), cub domain-containing protein 1 (CDCP1), fibroblast growth factor 21 (FGF-21), hepatocyte growth factor (HGF), IFN-γ, interleukin-18 receptor 1 (IL-18R1), monocyte chemotactic protein 3, and interleukin-12 (IL-2).
In the FMT arm, the levels of twelve proteins exhibited profound changes across all time points, encompassing tumor necrosis factor (TNF), CDCP1, IFN-γ, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), signaling lymphocytic activation molecule 1 (SLAMF1), cluster of differentiation 8a (CD8A), cluster of differentiation 5 (CD5), Fms-related tyrosine kinase 3 ligand (FLT3L), chemokine ligand 25 (CCL25), fibroblast growth factor-23 (FGF-23), cluster of differentiation 6 (CD6), and caspase-8. Notable differences in protein levels between FMT and sham-treated subjects 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 exhibited the most substantial positive impact on IFN-γ, Axin-1, and CCL25, while displaying the largest negative effects on CCL19 and IL-6.
These findings underscore the potential of FMT to modulate the gut microbiota-immune axis and alter inflammation-associated protein signatures. The potential synergistic effects of FMT with immunosuppressant medications or its ability to induce beneficial clinical outcomes by targeting microbial factors in immune-mediated arthritis will be crucial areas for future investigation.
RMD Open
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 et al.
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