Integrated Metagenomics and Transcriptomics Analysis Reveals Pathways Associated with Oral Periapical Lesions Formation and Progression

Periapical abscesses, radicular cysts, and periapical granulomas are among the most frequently identified pathological lesions in the alveolar bone. Although many studies have investigated bacterial metagenomics in periapical abscesses, little is known about the genome mining of abundant bacteria of periapical lesions and its correlation to human transcriptome. This study aims to explore the enriched metabolic environment of periapical lesions associated with microbial diversity and their role in lesion progression. Bacterial DNA and human RNA were isolated from periapical lesions and healthy pulp tissue and sequenced using next-generation sequencing. Bacterial sequences were then analyzed to identify secondary metabolites, pathogenic proteins, and their associated metabolic pathways. Integrated bacterial and human metabolic pathways indicated similar pathways in each lesion. Among these pathways, inflammatory response, humoral immune response, and hemopoiesis were enriched in abscesses. NABA matrisome associated, neutrophil degranulation, and P73 pathway were enriched in cysts. Meanwhile, response to bacterium, regulation of immune effector process, and positive regulation of response to external stimulus were enriched in granulomas. In conclusion, this study is the first to elucidate the interplay between microbial and human metabolic activity. These findings have significant clinical implications for the early diagnosis, prevention, and treatment of periapical lesions.