Does Systemic Inflammation Mediate Associations Between Gut Microbiome and Periodontitis?

Objectives: The gut microbiome has a strong symbiotic relationship with the human body and, potentially, also with the oral cavity. The relationship between the oral and gut microbiome might be bidirectional. Studies have suggested that alterations in the gut microbiome composition can lead to changes in the systemic inflammatory response, which may contribute to the development and progression of periodontitis.
Methods: We considered cross-sectional data from the Study of Health in Pomerania (SHIP-TREND-0; 2008-2012; N=4420). Stool samples were collected and sequenced via the MiSeq platform (Illumina, San Diego, USA). The microbiome dataset was recorded and assessed at the genus level. Genera significantly associated with periodontitis were selected via sparse principal component analysis (sPCA) and sparse partial least squares – discriminant analysis (sPLS-DA). Regression models were performed between all the genera selected in the first component and the inflammatory biomarkers such as C-reactive protein (CRP) levels, fibrinogen levels, and white blood count (WBC) from the entire dataset as well as the individual inflammatory biomarkers from the Bioplex panel utilising the SHIP-TREND-0 Premium subset data. P values were adjusted for multiple testing controlling the false discovery rate at 5%.
Results: Gut microbiome data and periodontal data were available for 3088 subjects. In total, 350 genera were identified. The microbiome differed significantly across CDC/AAP periodontitis groups (p<0.0001). Among genera associated with the CDC/AAP case definition, Holdemania and Solobacterium were found to be significantly associated with increased serum CRP (Beta=24.09 g/l (95% CI:6.47-41.71)) and fibrinogen levels (Beta=0.83 g/l (95% CI:0.08-1.58)). Furthermore, Alloprevotella and Solobacterium were significantly associated with increased IL-10 (Beta=0.05 (95% CI:0.01-0.09)) and MMP1 (Beta=11.12 (95%CI:1.81-20.44)) levels, respectively. However, all significant associations relating to systemic inflammatory markers were lost after accounting for multiple testing.
Conclusions: Associations of the gut microbiome with periodontitis were not explained by variations in systemic inflammation markers.