IgG sequencing maps systemic antibody binding to oral commensals and pathobionts in health and periodontitis

Abstract The oral cavity harbors one of the body’s most diverse microbial communities, which continuously seeds the bloodstream and gastrointestinal tract, particularly in periodontitis, a disease in which both barrier permeability and microbial burden increase. Despite this constant systemic exposure, overt bacteremia from oral organisms is rare, suggesting an active surveillance system that contains this reservoir. Here, we apply IgG-sequencing to comprehensively map mucosal and systemic antibody recognition of the oral microbiome across paired oral fluid and serum from healthy individuals and patients with periodontitis. We find that IgG-binding is only weakly predicted by microbial abundance, suggesting taxon-specific and largely conserved IgG-binding of commensals, many of them streptococci which dominate antibody recognition irrespective of disease state. Periodontitis broadens the repertoire of IgG-bound taxa to include particular disease-associated pathobionts while preserving robust targeting of health-associated symbionts. Comparison of salivary and serum antibody profiles further uncovers a subset of commensal streptococci, including species implicated in infective endocarditis, that acquire disproportionate systemic IgG binding in periodontitis. Together, these findings establish a taxon-level atlas of humoral immunosurveillance at a major mucosal-microbial interface and reveal how periodontal disease reshapes systemic antibody recognition of both pathobionts and commensals.