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
{"title":"An Intestinal Microbiome Intervention Affects Biochemical Disease Activity in Patients with Antiphospholipid Syndrome.","authors":"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","doi":"10.1055/s-0044-1788653","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background</b> 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. <b>Objective</b> To evaluate whether the gut microbiome affects disease activity in human APS. <b>Methods</b> 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. <b>Results</b> 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 ( <i>p</i> = 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 ( <i>p</i> = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. <b>Conclusion</b> The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"8 3","pages":"e308-e316"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300102/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"TH open : companion journal to thrombosis and haemostasis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/s-0044-1788653","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.