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.