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CC BY 4.0 · TH Open 2024; 08(03): e308-e316
DOI: 10.1055/s-0044-1788653
Original Article

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

Authors

  • Valérie L. B. I. Jansen

    1   Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
    2   Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
    3   Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands

  • Dagmar J. M. van Mourik

    2   Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
    4   Department of Experimental Vascular Medicine, Amsterdam UMC location AMC, University of Amsterdam, Amsterdam, The Netherlands
    5   Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands

  • Mark Davids

    4   Department of Experimental Vascular Medicine, Amsterdam UMC location AMC, University of Amsterdam, Amsterdam, The Netherlands

  • Kika van Bergen en Henegouwen

    1   Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands

  • Tessa Noordermeer

    6   Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands

  • Johannes H. M. Levels

    4   Department of Experimental Vascular Medicine, Amsterdam UMC location AMC, University of Amsterdam, Amsterdam, The Netherlands

  • Maarten Limper

    7   Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

  • Michiel Coppens

    1   Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
    2   Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands

  • Max Nieuwdorp

    1   Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands

  • Rolf T. Urbanus

    6   Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands

  • Saskia Middeldorp

    8   Department of Internal Medicine and Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, The Netherlands

  • Thijs E. van Mens

    1   Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
    2   Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
    3   Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
    5   Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands

Funding T.v.M. received a Clinical Scientist grant from the Dutch Heart Foundation (2020T013). This research was supported by an Out of the Box grant of Amsterdam Reproduction and Development. M.N. is supported by a personal ZONMW VICI grant 2020 (09150182010020).
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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.

Keywords

antiphospholipid syndrome - autoimmune disease - intestinal microbiome - gut microbiome

Author Statement

Valérie L.B.I. Jansen: methodology, investigation, data curation, project administration, writing—original draft; Dagmar J.M. van Mourik: investigation, data curation, writing—review and editing; Mark Davids: formal analysis, visualization, writing—review and editing; Kika van Bergen en Henegouwen: investigation, writing—review and editing; Tessa Noordermeer: investigation, writing—review and editing; Johannes H.M. Levels: investigation, writing—review and editing; Maarten Limper: resources, writing—review and editing; Michiel Coppens: project administration, writing—review and editing; Max Nieuwdorp: resources, writing—review and editing; Rolf T. Urbanus: investigation, resources, writing—review and editing; Saskia Middeldorp: supervision, writing—review and editing; Thijs E van Mens: conceptualization, methodology, formal analysis, data curation, supervision, project administration, funding acquisition, writing—review and editing. Biomarkerpanel and gut microbiota data are publicly accessible via: Mendeley Data, V1, doi: 10.17632/zxsjyjfzjd.1.


Supplementary Material



Publication History

Received: 09 April 2024

Accepted: 29 June 2024

Article published online:
05 August 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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