@article{Kragsnaes:2023:10.1002/acr2.11604,
author = {Kragsnaes, MS and Miguens, Blanco J and Mullish, BH and Contreras, Serrano JI and Kjeldsen, J and Horn, HC and Pedersen, JK and Munk, HL and Nilsson, AC and Salam, A and Lewis, MR and Chekmeneva, E and Kristiansen, K and Marchesi, JR and Ellingsen, T},
doi = {10.1002/acr2.11604},
journal = {ACR Open Rheumatology},
pages = {583--593},
title = {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},
url = {http://dx.doi.org/10.1002/acr2.11604},
volume = {5},
year = {2023}
}

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TY  - JOUR
AB  - ObjectiveWe 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).MethodsThis 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.ResultsTrial 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).ConclusionIntestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.
AU  - Kragsnaes,MS
AU  - Miguens,Blanco J
AU  - Mullish,BH
AU  - Contreras,Serrano JI
AU  - Kjeldsen,J
AU  - Horn,HC
AU  - Pedersen,JK
AU  - Munk,HL
AU  - Nilsson,AC
AU  - Salam,A
AU  - Lewis,MR
AU  - Chekmeneva,E
AU  - Kristiansen,K
AU  - Marchesi,JR
AU  - Ellingsen,T
DO  - 10.1002/acr2.11604
EP  - 593
PY  - 2023///
SN  - 2578-5745
SP  - 583
TI  - 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
T2  - ACR Open Rheumatology
UR  - http://dx.doi.org/10.1002/acr2.11604
UR  - https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.11604
UR  - http://hdl.handle.net/10044/1/106258
VL  - 5
ER  - 

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