High-performing cross-dataset machine learning reveals robust microbiota alteration in secondary apical periodontitis

Multiple research groups have consistently underscored the intricate interplay between the microbiome and apical periodontitis. However, the presence of variability in experimental design and quantitative assessment have added a layer of complexity, making it challenging to comprehensively assess the relationship. Through an unbiased methodological refinement analysis, we re-analyzed 4 microbiota studies including 120 apical samples from infected teeth (with/without root canal treatment), healthy teeth, using meta-analysis and machine learning. With high-performing machine-learning models, we discover disease signatures of related species and enriched metabolic pathways, expanded understanding of apical periodontitis with potential therapeutic implications. Our approach employs uniform computational tools across datasets to leverage statistical power and define a reproducible signal potentially linked to the development of secondary apical periodontitis (SAP).