Impact of electronic cigarette use on the oral microbiome: a protocol for a systematic review of clinical studies

Background: The oral microbiome plays a pivotal role in maintaining both oral and systemic health, yet it can be disrupted by lifestyle factors such as tobacco use. Electronic cigarette (e-cig) has emerged as a popular alternative to conventional smoking, often perceived as a harm reduction tool. While combustible tobacco smoking is known to promote pathogenic shifts in the oral microbiota, evidence on the impact of e-cig use remains limited and inconsistent. A systematic synthesis of current evidence is therefore warranted to assess the potential microbiological and clinical implications of e-cig use. This systematic review aims to critically evaluate clinical studies assessing the effects of e-cig use on the oral microbiome, with specific comparisons to current smokers and never smokers. Methods: PubMed, Scopus, and Web of Science have been searched from 2010 up to August 27, 2025, using MeSH terms and free-text keywords related to e-cigs, vaping, oral microbiome, and microbial diversity. Eligible studies will include randomized controlled trials, cross-sectional, and longitudinal observational designs comparing e-cig users with current smokers and/or never smokers, and using culture-independent, next-generation sequencing techniques for microbiome profiling. Two reviewers will independently perform study selection, data extraction, and quality assessment using the Joanna Briggs Institute critical appraisal tools. Given expected heterogeneity, findings will be synthesized narratively and tabulated; subgroup analyses will examine differences according to oral health status, e-cig use patterns, and sampling site. Results: Database searching was completed on Aug 27, 2025, and identified 39 records in PubMed, 46 in Scopus, and 83 in Web of Science. Secondary searches, including gray literature screening and snowballing, have not yet been conducted. Screening and selection of retrieved articles are in progress, with review completion expected by November 2025. Discussion: This review is expected to provide a comprehensive and critical appraisal of the current evidence on the relationship between e-cig use and oral microbiome composition. By summarizing key microbial diversity patterns, identifying taxa-level differences, and highlighting methodological strengths and limitations, it will clarify the extent to which e-cig use may influence oral microbial communities. The anticipated heterogeneity in study designs, outcome measures, and sampling methods underscores the need for cautious interpretation and for standardization in future research. The findings aim to inform clinical understanding of potential local and systemic implications of e-cig use and to guide the design of robust, longitudinal studies with careful control of residual confounding. Systematic review registration: PROSPERO registration: CRD420251120281.