Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

Maja Skov Kragsnaes, Jesus Miguens Blanco, Benjamin H. Mullish, Jose Ivan Contreras-Serrano, Jens Kjeldsen, Hans Christian Horn, Jens Kristian Pedersen, Heidi Lausten Munk, Anna Christine Nilsson, Ash Salam, Matthew R. Lewis, Elena Chekmeneva, Karsten Kristiansen, Julian R. Marchesi*, Torkell Ellingsen

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Abstract

Objective: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT). Methods: This exploratory study is based on the FLORA trial cohort, in which 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, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance. Results: Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02). Conclusion: Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

OriginalsprogEngelsk
TidsskriftACR Open Rheumatology
Vol/bind5
Udgave nummer11
Sider (fra-til)583-593
ISSN2578-5745
DOI
StatusUdgivet - nov. 2023

Bibliografisk note

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. The National Phenome Centre was supported by the Medical Research Council and National Institute for Health Research (NIHR) (grant MC_PC_12025), infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). Drs. Miguens Blanco and Marchesi, the Division of Digestive Diseases, and the MRC NIHR National Phenome Centre at Imperial College London receive financial and infrastructure support from the NIHR BRC based at Imperial College Healthcare NHS Trust and Imperial College London. Dr. Miguens Blanco's work was supported by a grant from Versus Arthritis (formerly Arthritis Research UK) under the Phenomic characterization of Psoriatic Arthritis: MI‐PART project (21228). Dr. Mullish is recipient of an NIHR Academic Clinical Lectureship (CL‐2019‐21‐002).

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