Microbes and microbial metabolites as immunometabolic drivers of the oral potentially malignant disorder microenvironment
Abstract
Oral potentially malignant disorders (OPMDs) give rise to most oral squamous cell carcinomas (OSCC). Around 8% transform, but no one can tell which. Dysplasia grade, the instrument in current use, varies between observers and predicts transformation poorly, and the burden falls disproportionately on South and Southeast Asia. The oral microbiome is increasingly implicated in the premalignant microenvironment, but the literature is largely compositional: it records which organisms are present without measuring what they do to local immunity. This scoping review maps the evidence published between January 2015 and June 2026 on microbial composition, microbial metabolites and immune phenotype in human OPMD and OSCC, asking specifically where these have been measured in the same lesion. Only oral studies are charted. Mechanisms established in colorectal, melanoma and other tumour models are excluded, so that every claim about OPMD is answerable from oral data. One qualification is pre-specified: organisms native to the oral biofilm, Fusobacterium nucleatum foremost among them, are also enriched in tumours elsewhere, and such studies may be cited as evidence about the organism, labelled as deriving from another tumour type and excluded from the charted record. The expected consequence, accepted in advance, is that the review will describe what has been measured in OPMD without being able to evidence a mechanism from it. That asymmetry is itself the finding. Outputs. A map of the charted evidence by measurement domain; the Immunometabolic Field Hypothesis, a four-stage hypothesis-generating model; and the Oral Immunometabolic Risk Index, a prediction model for malignant transformation specified in advance with explicit falsification criteria. Design. Scoping review per JBI guidance, reported per PRISMA-ScR with record flow in PRISMA 2020 format. PubMed/MEDLINE, Scopus and Web of Science. Dual independent screening and charting. No risk-of-bias appraisal and no meta-analysis. Team. Samapika Routray and Suchanda Sahu, All India Institute of Medical Sciences, Bhubaneswar. No funding. No conflicts of interest.
