Biology subjects

Moutsopoulos, N.

Publications and source records attributed to Moutsopoulos, N..

4 recordsLinked to original sources

bioRxiv2026

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

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.

immunology↗

bioRxiv2026

Mucosal Inflammation Shapes Human Neutrophil States in Tissue and Circulation

The oral mucosa is a prototypical human barrier reliant on neutrophils for homeostasis, as both neutrophil deficiency and excessive activation are linked to immunopathology. Yet, whether neutrophils acquire tissue-specific states in health or disease remains unclear. We incorporated single-cell RNA sequencing, spectral flow cytometry, and spatial proteomics across tooth-associated oral mucosa (gingiva) and interconnected compartments of blood and oral cavity to define neutrophil tissue specification in healthy individuals and patients with periodontitis, a neutrophil-dominated inflammatory disease. In health, mucosal neutrophils adopt discrete immunoregulatory states despite constant microbial exposure and mechanical injury. Periodontitis disrupts these programs through infiltration of blood-like neutrophil subsets, increased transcriptional noise, and heightened effector activation. Strikingly, oral inflammation systemically imprints on circulating neutrophils, marked by the expansion of a Rho-GTPase regulatory program that is shared across diverse human inflammatory conditions. Together, these findings establish a framework for understanding how localized tissue inflammation affects both neutrophil plasticity at barrier surfaces and conditioning of systemic neutrophil states with broad implications for inflammatory disease pathogenesis.

immunology↗

bioRxiv2024

Quantitative mapping of pseudouridines in bacteria RNA

RNA pseudouridylation is one of the most prevalent post-transcriptional modifications, occurring universally across all organisms. Although pseudouridines have been extensively studied in bacterial tRNAs and rRNAs, their presence and role in bacterial mRNA remain poorly characterized. Here, we used a bisulfite-based sequencing approach to provide a comprehensive and quantitative measurement of bacteria pseudouridines. As a proof of concept in E. coli, we identified 1,954 high-confidence sites in 1,331 transcripts, covering almost 30% of the transcriptome. Furthermore, pseudouridine mapping enabled the detection of differentially expressed genes associated with stress response that were unidentified using conventional RNA-seq approach. We also demonstrate that in addition to pseudouridine profiling, our approach can facilitate the discovery of previously unidentified transcripts. As an example, we identified a small RNA transcribed from the antisense strand of tRNA-Tyr which represses expression of distal genes. Finally, we mapped pseudouridines in oral microbiome samples of human subjects, demonstrating the broad applicability of our approach in complex microbiomes. Altogether, our work highlights the advantages of mapping bacterial pseudouridines and provides a tool to study posttranscription regulation in microbial communities.

microbiology↗

bioRxiv2020

A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen

Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizer Veillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state.

microbiology↗