Exploring Streptococcus sanguinis Extracellular Vesicles as Regulators of Gingival Homeostasis and Periodontal Defense

Oral commensal streptococci, particularly Streptococcus sanguinis (Ss), play a crucial role in maintaining immune balance and tissue homeostasis within the oral cavity. As early colonizers of dental biofilms, these bacteria contribute to immune system priming and regulate host responses to microbial communities. While generally associated with oral health, Ss also exhibits pro-inflammatory traits, highlighting a dual role in both promoting and modulating immune activity. Our preliminary data reveal that this duality is promoted through the release of extracellular membrane vesicles (EMVs), which influence host cell signaling, gene expression, and epithelial integrity. The overarching goal of this project is to define how Ss EMVs contribute to immune regulation, apoptosis prevention, and epithelial barrier maintenance. We hypothesize that EMVs serve as key molecular effectors of commensal function, and their production and activity are shaped by ecological and host-associated factors. Aim 1 will assess how environmental conditions and disease states influence EMV production and cargo using clinical Ss isolates. Aim 2 will investigate how Ss EMVs enter oral epithelial cells, trigger immune responses, and how specific EMV components mediate host interactions. Aim 3 will evaluate the ability of Ss EMVs to prevent pathogen-induced apoptosis and preserve epithelial integrity in both monolayer and 3D tissue models. This research will advance our understanding of streptococcal molecular commensalism, reveal mechanisms of EMV-mediated host protection, and establish a foundation for novel strategies to support oral health through microbial EMV-based therapies. Project Number: 1R01DE035736-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Jens Kreth | Institution: OREGON HEALTH & SCIENCE UNIVERSITY, PORTLAND, OR | Award Amount: $524,669 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 MSOS-T (02)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11316420