Oral microbiome and Porphyromonas gingivalis

The oral microbiome comprises roughly 700 bacterial taxa colonising teeth, gingival sulcus, tongue and mucosa. Porphyromonas gingivalis is a Gram-negative anaerobe widely described as a keystone pathogen of periodontitis: even at low relative abundance it can drive dysbiosis and chronic inflammation. Beyond the mouth, periodontitis has been associated with cardiovascular disease, type 2 diabetes and adverse pregnancy outcomes. In 2019 Dominy and colleagues reported P. gingivalis DNA and its gingipain proteases in post-mortem Alzheimer brains, with gingipain levels correlating with tau and ubiquitin pathology; small-molecule gingipain inhibitors reduced bacterial load and neuroinflammation in mouse models. The follow-up Phase 2/3 GAIN trial of the gingipain inhibitor atuzaginstat (COR388) missed its co-primary endpoints at topline readout in October 2021, and the FDA placed it on full clinical hold for hepatotoxicity in January 2022, with the final negative readout in Q1 2022, so causality in humans remains unproven; the work nonetheless reinforced interest in oral health as a modifiable systemic exposure.