Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Introduction An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.
Methods and analysis This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.
Ethics and dissemination No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.
PROSPERO registration number CRD42025644244.
Data availability statement
No data are available.
Methods and analysis This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.
Ethics and dissemination No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.
PROSPERO registration number CRD42025644244.
Data availability statement
No data are available.
Date Issued
2025-12-01
Date Acceptance
2025-11-21
Citation
BMJ Open, 2025, 15 (12)
ISSN
2044-6055
Publisher
BMJ Publishing Group
Journal / Book Title
BMJ Open
Volume
15
Issue
12
Copyright Statement
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group
License URL
Identifier
http://bmjopen.bmj.com/content/15/12/e101593.abstract
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
RHEUMATOLOGY
Microbiota
Antibiotics
Inflammation
Systematic Review
Meta-Analysis
INTERNATIONAL SCIENTIFIC ASSOCIATION
CONSENSUS STATEMENT
PROBIOTICS
ARTHRITIS
GUIDELINES
PREBIOTICS
SCOPE
Publication Status
Published
Coverage Spatial
England
Article Number
e101593
Date Publish Online
2025-12-14