Microbial functional pathways based on metatranscriptomic profiling enable effective saliva-based health assessments for precision wellness

It is increasingly recognized that an important step towards improving overall health is to accurately measure biomarkers of health from the molecular activities prevalent in the oral cavity. We present a general methodology for computationally quantifying the activity of microbial functional pathways using metatranscriptomic data. We describe their implementation as a collection of eight oral pathway scores using a large salivary sample dataset (n=9,350), and we evaluate score associations with oropharyngeal disease phenotypes within an unseen independent cohort (n=14,129). As clinical validation, we show that the relevant oral pathway scores are significantly worse in individuals with periodontal disease, acid reflux, and nicotine addiction, compared with controls. Given these associations, we make the case to use these oral pathway scores to provide molecular health insights from simple, non-invasive saliva samples, and as molecular endpoints for actionable interventions to address the associated conditions. Highlights Microbial functional pathways in the oral cavity are quantified as eight oral scores Scores are significantly worse for individuals with oropharyngeal disease phenotypes This methodology may be generalized to other pathways and other sample types These scores provide longitudinal health insights in a precision wellness application Graphical Abstract