An Intestinal Microbiome Intervention Affects Biochemical Disease Activity in Patients with Antiphospholipid Syndrome.

Valérie L B I Jansen, Dagmar J M van Mourik, Mark Davids, Kika van Bergen En Henegouwen, Tessa Noordermeer, Johannes H M Levels, Maarten Limper, Michiel Coppens, Max Nieuwdorp, Rolf T Urbanus, Saskia Middeldorp, Thijs E van Mens
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Abstract

Background  The origin of autoantibodies in patients with antiphospholipid syndrome (APS) is unknown. The gut microbiome contributes to autoimmunity and contains peptide homologues to the main APS autoantigen, which affect disease activity in animal models. Alteration of the gut microbiota with vancomycin diminishes disease activity in mice but no data on the effect of gut microbiota alteration in APS patients are available to date. Objective  To evaluate whether the gut microbiome affects disease activity in human APS. Methods  This was a pre-post design intervention study in APS patients with stable disease and no gastrointestinal comorbidity. Subjects received oral vancomycin, 500 mg four times daily for 7 days, previously shown to alter gut microbiota composition without systemic effects. Disease activity was assessed at four time points by measuring a panel of clinical phenotype-related biomarkers: antiphospholipid antibodies (APLAs), complement and inflammation markers, and hemostatic parameters. The primary outcome was the composite of the biomarker panel determined by multilevel principal component analysis. Results  A total of 15 subjects completed the study. The primary outcome, the first principal component of the biomarker panel data, was significantly different after 7 days of vancomycin treatment ( p  = 0.03), but not at day 42. APLA titers were unaffected. Unexpectedly, 4 out of 15 patients were negative for APLAs at baseline. In a post-hoc analysis, there was a prolonged effect for subjects with positive antibodies at baseline ( p  = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. Conclusion  The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.

肠道微生物组干预可影响抗磷脂综合征患者的生化疾病活动。
背景 抗磷脂综合征(APS)患者自身抗体的来源尚不清楚。肠道微生物群有助于自身免疫,并含有与主要 APS 自身抗原同源的多肽,这些多肽会影响动物模型的疾病活动。用万古霉素改变肠道微生物群可降低小鼠的疾病活动性,但迄今为止还没有关于改变肠道微生物群对 APS 患者影响的数据。目的 评估肠道微生物群是否会影响人类 APS 的疾病活动。方法 这是对病情稳定、无胃肠道合并症的 APS 患者进行的一项前-后设计干预研究。受试者口服万古霉素(500 毫克,每日四次,共 7 天),之前的研究表明万古霉素可改变肠道微生物群的组成,但不会产生全身性影响。在四个时间点通过测量一组临床表型相关的生物标志物来评估疾病活动性:抗磷脂抗体(APLA)、补体和炎症标志物以及止血参数。主要结果是通过多级主成分分析确定的生物标记物组合。结果 共有 15 名受试者完成了研究。主要结果是生物标记物面板数据的第一个主成分在万古霉素治疗 7 天后有显著差异(p = 0.03),但在第 42 天时没有差异。APLA 滴度未受影响。意想不到的是,15 名患者中有 4 名在基线时 APLA 呈阴性。在事后分析中,基线抗体呈阳性的受试者的疗效延长(p = 0.03)。而对于基线抗体为阴性的受试者,干预没有效果。结论 肠道微生物群会影响 APS 患者的生化疾病活动。其机制尚不清楚,但似乎具有 APS 特异性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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