Kragsnaes Maja Skov, Miguens Blanco Jesus, Mullish Benjamin H, Serrano-Contreras Jose Ivan, Kjeldsen Jens, Horn Hans Christian, Pedersen Jens Kristian, Munk Heidi Lausten, Nilsson Anna Christine, Salam Ash, Lewis Matthew R, Chekmeneva Elena, Kristiansen Karsten, Marchesi Julian R, Ellingsen Torkell
Odense University Hospital and University of Southern Denmark, Odense, Denmark.
Imperial College London, London, UK.
ACR Open Rheumatol. 2023 Nov;5(11):583-593. doi: 10.1002/acr2.11604. Epub 2023 Sep 22.
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).
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 H Nuclear Magnetic Resonance.
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).
Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.
我们研究了甲氨蝶呤治疗的活动性银屑病关节炎（PsA）患者的肠道通透性以及粪便、血浆和尿液的代谢组学特征，以及这与一次假手术或粪便微生物群移植（FMT）后的临床反应之间的关系。
这项探索性研究基于FLORA试验队列，该队列纳入了31例尽管接受了至少3个月甲氨蝶呤治疗但外周PsA疾病活动度为中到高的患者，进行了一项为期26周的双盲、1:1随机、假手术对照试验。参与者通过胃镜随机分配接受一次健康供体FMT（n = 15）或假手术（n = 16）。主要试验终点是26周内治疗失败的比例。我们在基线（n = 31）和第26周（n = 26）进行了乳果糖与甘露醇比值（LMR）试验，以评估小肠通透性。使用氢核磁共振测量在基线、第4周、第12周和第26周收集的粪便、血浆和尿液样本中的代谢组学特征。
在第26周时，试验失败组（n = 7）的LMR显著高于反应者组（n = 19）（0.027[0.017 - 0.33]对0.012[0 - 0.064]，P = 0.013），表明肠道通透性增加。多变量分析显示，基于反应者（n = 19）和失败组（n = 12）在所有时间点的粪便（P < 0.0001）和血浆（P = 0.005）代谢组学特征，有一个显著的模型，而两组之间尿液代谢组学特征没有差异（P = 1）。粪便N - 乙酰糖蛋白GlycA与健康评估问卷残疾指数相关（系数 = 0.50；P = 0.03），粪便丙酸与第26周时美国风湿病学会2（ACR2）反应相关（系数 = 27，P = 0.02）。
PsA患者的肠道通透性以及粪便和血浆代谢组学特征与主要临床试验终点（失败与反应者）相关。
