Multi-Site Analysis of Biosynthetic Gene Clusters (BGCs) from the Periodontitis Oral Microbiome

Bacteria are key modulators of human health and disease. Biochemicals synthesized by bacterial biosynthetic gene clusters (BGCs) have been shown to play key roles in microbiome–host and microbe–microbe interactions. Whilst BGCs have been widely investigated in the human gut, very few studies have explored BGCs within oral niches. In this pilot study, we used shotgun metagenomic sequencing to profile the microbiota from three different oral sites: saliva, subgingival plaque, and supragingival plaque, within subjects with periodontitis (n = 23) versus controls (n = 16). Our aim was to identify BGCs associated with periodontitis, as well as BGCs that exhibited site (niche) selectivity. We identified 10,742 BGCs in the cohort, some of which were unique for a specific oral site. Aryl polyenes (APEs) and Bacteriocin were the most prevalent clusters, but we also found several ‘novel’ BGCs that were widely distributed across diverse bacterial phyla; other BGCs exhibited selectivity for periodontitis niches. Taken together, our findings significantly expand our metagenomic understanding of microbiota within healthy and diseased oral niches. By uncovering previously unexplored biosynthetic pathways, we provide a potential road-map for the future exploration of poorly understood host-microbe and microbe-microbe interactions in the oral cavity that may contribute to periodontitis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the university of Hong Kong internal fund (Seed Fund for Basic Research for New Staff). ### Author Declarations 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: Ethics committee/IRB of Hong Kong/Hospital Authority Hong Kong West Cluster gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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). Yes 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 All data produced are available online at NCBI database (BioProject accession numbers: PRJNA932553). [https://figshare.com/projects/Systematic\_Analysis\_of\_Site-Specific\_Biosynthetic\_Gene\_Clusters\_BGCs\_of\_Oral\_Microbiome\_in\_Periodontitis/157008][1] [1]: https://figshare.com/projects/Systematic_Analysis_of_Site-Specific_Biosynthetic_Gene_Clusters_BGCs_of_Oral_Microbiome_in_Periodontitis/157008