Modelling of the Systemic Inflammatory Host Response in Relation to the Microbiome of the Endodontic Infection

Aim: This study aimed to investigate systemic inflammatory responses in individuals with apical periodontitis (AP) compared to age-matched healthy controls, using advanced multiway modelling techniques. We examined associations between inflammatory mediators, age, gender, symptomatic status, and the microbial composition and function to better understand host–microbe interactions in AP. Methods: We conducted a longitudinal study with 53 participants (27 with AP, 26 controls) aged 18 to 80. Blood inflammatory mediators were measured at multiple time points. Root canal microbiome and potential functions were analysed using 16S rRNA gene sequencing. Data were analysed using Parallel Factor Analysis (PARAFAC) and Advanced Coupled Matrix and Tensor Factorization (ACMTF) to capture time-resolved variation. Results: PARAFAC revealed that IL-4 levels were significantly elevated in AP cases, suggesting a role for adaptive immune activation. Age strongly influenced markers such as CRP, TNF-α, and VEGF. Symptomatic AP cases showed higher CRP and lower OPG levels, indicating more active inflammation and altered bone metabolism. ACMTF identified associations between specific taxa (e.g., Parvimonas micra, Streptococcus mutans) and inflammatory mediators, with functional analysis highlighting enriched pathways like sphingolipid signalling in asymptomatic cases. Conclusion: This study provides novel insights into the systemic immune profile of individuals with AP. IL-4 and bone metabolism markers may serve as potential biomarkers for distinguishing AP status. Our findings support the relevance of systemic inflammation in endodontic infections and underscore the value of multi-marker, multivariate approaches to better characterise disease progression and host–microbiome interactions. Such insights could contribute to improved risk stratification and personalised management in dental and systemic health contexts.