Multi-site analysis of biosynthetic gene clusters from the periodontitis oral microbiome.

Bacteria significantly influence human health and disease, with bacterial biosynthetic gene clusters (BGCs) being crucial in the microbiome-host and microbe-microbe interactions. Despite extensive research into BGCs within the human gut microbiome, their roles in the oral microbiome are less understood. This pilot study utilizes high-throughput shotgun metagenomic sequencing to examine the oral microbiota in different niches, particularly focusing on the association of BGCs with periodontitis. We analysed saliva, subgingival plaque and supragingival plaque samples from periodontitis patients (=23) and controls (=16). DNA was extracted from these samples using standardized protocols. The high-throughput shotgun metagenomic sequencing was then performed to obtain comprehensive genetic information from the microbial communities present in the samples. Our study identified 10 742 BGCs, with certain clusters being niche-specific. Notably, aryl polyenes and bacteriocins were the most prevalent BGCs identified. We discovered several 'novel' BGCs that are widely represented across various bacterial phyla and identified BGCs that had different distributions between periodontitis and control subjects. Our systematic approach unveiled the previously unexplored biosynthetic pathways that may be key players in periodontitis. Our research expands the current metagenomic knowledge of the oral microbiota in both healthy and periodontally diseased states. These findings highlight the presence of novel biosynthetic pathways in the oral cavity and suggest a complex network of host-microbe and microbe-microbe interactions, potentially influencing periodontal disease. The BGCs identified in this study pave the way for future investigations into the role of small-molecule-mediated interactions within the human oral microbiota and their impact on periodontitis.