Salivary microbiome responses to chlorhexidine and Coriandrum sativum essential oil mouthwashes in patients with periodontitis in a randomized 2-week clinical trial

Objectives To compare the short-term salivary microbiome effects of a Coriandrum sativum essential oil (CSEO) mouthwash, chlorhexidine (CHX) as a benchmark comparator, and water in patients with periodontitis.Materials and methods In this randomized three-arm trial, participants with periodontitis rinsed twice daily for 14 days with water, CSEO, or 0.12% CHX. Preclinical anti-Porphyromonas gingivalis and fibroblast cytotoxicity assays informed CSEO concentration selection. Shotgun metagenomic sequencing was performed on 54 saliva libraries, two per participant, from 27 participants sampled at baseline and week 2 (H2O n = 9, CSEO n = 8, CHX n = 10). Alpha diversity, within-subject Bray-Curtis change, and differential abundance were analysed longitudinally.Results Both active agents inhibited P. gingivalis in vitro, with CHX showing greater potency. In the clinical trial, no statistically detectable difference between CSEO and water was observed for the primary species-level Bray-Curtis outcome (q = 0.413), alpha diversity (all q ≥ 0.259), or differential abundance. CHX showed greater species-level Bray-Curtis change than water (q = 0.020), lower species-level Simpson diversity (q = 0.014), and broad taxonomic restructuring.Conclusions Under the tested formulation and exposure conditions, CSEO did not produce a statistically detectable group-level salivary microbiome shift relative to water. CHX provided a benchmark for broad ecological perturbation. The CSEO null finding does not exclude modest or heterogeneous effects in a larger cohort.Clinical relevance No clinical benefit can be inferred from the absence of a detectable CSEO-associated microbiome shift. Larger studies integrating clinical, inflammatory, and direct functional outcomes are needed.Trial registration ISRCTN79156900, retrospectively registered on 11 May 2026.