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.

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.

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.

CRD42025644244.

The rise of electronic nicotine delivery systems (ENDS) has introduced new challenges to tobacco control and regulation, particularly among young adults, raising questions about their safety. This umbrella review aimed to synthesise existing systematic reviews with or without meta-analyses to evaluate the health impacts of ENDS.

We conducted a systematic literature search via the PICO strategy across multiple databases, focusing on e-cigarettes, ENDS and e-liquids, while excluding non-nicotine e-cigarette and nicotine replacement therapies (NRTs). Health outcomes include a range of clinical diseases and physiological changes. Quality assessment was performed via assessing the methodoligcal quality of systematic reviews 2 (AMSTAR-2), and the findings were synthesised narratively and in tables, prioritising the highest-rated reviews. The meta-analyses used R software (V.4.3) random effects models, and evidence quality was assessed via the Grading of Recommendations, Assessment, Development and Evaluation criteria.

Of the 5055 records, 69 systematic reviews were included. Systematic reviews have indicated increased risks of cardiovascular and respiratory diseases, mental health issues and substance abuse with ENDS use, especially among adolescents. Cardiovascular risk factors included increased heart rate (mean difference (MD) 1.41, 95% CI 0.81 to 2.01, I²=91%) from 25 studies; increased blood pressure (MD for systolic blood pressure=0.51 mm Hg, 95% CI 0.26 to 0.75, I²=89%; MD for diastolic blood pressure=0.59 mm Hg, 95% CI 0.35 to 0.83, I²=82%) from 23 studies; endothelial dysfunction and increased platelet activity. Respiratory risk factors included reduced lung function and a higher incidence of asthma in nine studies (OR 1.30, 95% CI 1.1 to 1.55; I²=43%) and chronic obstructive pulmonary disease. Mental health concerns, such as depression and suicidality, were also prevalent among adolescent ENDS users. Nine studies reported a negative effect of ENDS on periodontal health. Evidence of carcinogens has been found in the urinary examinations of ENDS users in some studies. The adverse events reported in seven randomised controlled trials with 2611 participants were similar between ENDS and NRT (RR 1.13, 95% CI 0.83 to 1.54, I²=12%).

Exposure to ENDS is harmful to various organ systems, especially cardiovascular and respiratory systems. Comprehensive regulatory measures and public health strategies are necessary to curb the use of ENDS, particularly among young people.