Objective This study utilizes small-sample periodontitis data to exploratively investigate causal relationships between the oral microbiome and periodontitis in East Asian populations. We aimed to identify specific oral microbial taxa that may drive disease pathogenesis. Given the exploratory nature of the dataset, findings should be interpreted as hypothesis-generating.

Methods We performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics for tongue dorsum and salivary microbiomes alongside periodontitis data in East Asian populations. Primary causal estimates were derived using the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode methods. To ensure robustness, we assessed heterogeneity using Cochran’s Q test, evaluated horizontal pleiotropy via the MR-Egger intercept and MR-PRESSO tests, and applied Steiger filtering to rule out reverse causality.

Results We identified 60 species-level microbial taxa causally associated with periodontitis, comprising 29 negative and 31 positive associations. These taxa were predominantly enriched within the genera Campylobacter, Pauljensenia, Solobacterium, and Streptococcus.

Conclusion This study provides tentative evidence for causal links between specific species-level oral microbial taxa and periodontitis, highlighting potential targets for prevention and therapeutic intervention.

The authors have declared no competing interest.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study used ONLY openly available human data that were originally located at: GWAS summary statistics for salivary and dorsal tongue microbiota: CNP0001664, publicly available from the China National GeneBank (CNGB) database at https://db.cngb.org/search/project/CNP0001664/. GWAS summary statistics for periodontitis: GCST90478258, publicly available from the GWAS Catalog at https://www.ebi.ac.uk/. All datasets consist of de-identified summary-level statistics that were openly accessible to the public without any registration or application requirements prior to the initiation of this study.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The GWAS summary data for salivary and dorsal tongue microbiota are sourced from CNP0001664 (CNGB database: https://ftp2.cngb.org/). The GWAS summary data for periodontitis analyzed in the current study are sourced from GCST90478258 (GWAS Catalog: https://www.ebi.ac.uk/gwas/).