Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2026

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2026.1762187

PMID

41798927

PMCID

PMC12963321

PubMedCentral® Posted Date

2-20-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Periodontitis is a biofilm-induced chronic inflammatory disease, characterized by gingival inflammation and alveolar bone loss. According to a national survey, approximately half of the U.S. adults are affected by periodontal disease. To effectively prevent and treat periodontitis, it is essential to address its underlying causes. The primary etiological factors include polymicrobial synergy and dysbiosis of the oral microbiota, and a dysregulated immune response. The standard therapeutic approach, mechanical removal of biofilm through debridement, sometimes demonstrates limited efficacy, particularly in cases of severe periodontitis, which may require adjunctive or additional therapy. Emerging evidence indicates that periodontal tissue destruction is initiated by biofilm but primarily driven by a sustained, dysregulated host inflammatory response characterized by excessive cytokine production, osteoclast activation, and impaired inflammation resolution. In recent years, research has focused on targeting both the oral microbiota and immune response by utilizing antimicrobial therapeutics to diminish bacterial load and by modulating immune activity. Specifically, host modulation therapies (HMTs), such as the delivery of anti-inflammatory cytokines, nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose doxycycline, and lipid mediators, via various techniques, have been explored. However, challenges associated with its use encompass adverse effects resulting from prolonged administration, and systemic delivery methods are associated with an elevated risk of infection and the potential development of malignancy, as well as the disease rebound after cessation of treatment. This review examines current trends in HMTs for periodontitis and identifies potential limitations of these approaches. The insights gained may contribute to the development of improved strategies to enhance periodontal treatment outcomes.

Keywords

Humans, Periodontitis, Animals, Biofilms, Cytokines, Dysbiosis, cytokines, drug delivery systems, genetics, microbial, immunomodulation, periodontitis

Published Open-Access

yes

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