# Host modulation therapy in periodontitis: from established therapies to emerging technologies

**Authors:** Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, Simon Young, Chun-Teh Lee

PMC · DOI: 10.3389/fimmu.2026.1762187 · Frontiers in Immunology · 2026-02-20

## TL;DR

Periodontitis is a chronic gum disease caused by bacteria and immune response, and new therapies aim to target both bacteria and inflammation to improve treatment.

## Contribution

This review highlights current host modulation therapies for periodontitis and identifies their limitations to guide future improvements.

## Key findings

- Periodontitis is driven by microbial dysbiosis and excessive host inflammation.
- Current host modulation therapies have limitations including adverse effects and disease rebound.
- Emerging strategies aim to target both oral microbiota and immune response for better outcomes.

## 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.

## Linked entities

- **Chemicals:** doxycycline (PubChem CID 54671203)
- **Diseases:** periodontitis (MONDO:0005076)

## Full-text entities

- **Genes:** TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, ROCK2 (Rho associated coiled-coil containing protein kinase 2) [NCBI Gene 9475] {aka ROCK-II}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, MMP8 (matrix metallopeptidase 8) [NCBI Gene 4317] {aka CLG1, HNC, MMP-8, PMNL-CL}, DDIT3 (DNA damage inducible transcript 3) [NCBI Gene 1649] {aka AltDDIT3, C/EBPzeta, CEBPZ, CHOP, CHOP-10, CHOP10}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351] {aka COX, COX8, COX8-2, COX8L, MC4DN15, VIII}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, SGK1 (serum/glucocorticoid regulated kinase 1) [NCBI Gene 6446] {aka SGK}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}
- **Diseases:** cGVHD (MESH:D000092122), oral diseases (MESH:D009059), autoimmune disorders (MESH:D001327), oral carcinoma (MESH:D009062), immune-mediated diseases (MESH:C567355), genetic (MESH:D030342), alveolar (MESH:D002282), attachment loss (MESH:D017622), tooth loss (MESH:D016388), fibrosis (MESH:D005355), Periodontitis (MESH:D010518), gingival inflammation (MESH:D007249), cancer (MESH:D009369), diabetes mellitus (MESH:D003920), dysbiosis (MESH:D064806), cystic fibrosis (MESH:D003550), inflammatory bowel disease (MESH:D015212), periodontal disease (MESH:D010510), immune dysregulation (OMIM:614878), infectious diseases (MESH:D003141), rheumatoid arthritis (MESH:D001172), colorectal cancer (MESH:D015179), colitis (MESH:D003092), gastrointestinal and cardiovascular (MESH:D005767), infection (MESH:D007239), Cardiovascular disease (MESH:D002318), HMT (MESH:D016609), Crohn's (MESH:D003424), toxicities (MESH:D064420), alveolar bone loss (MESH:D016301), bone loss (MESH:D001847)
- **Chemicals:** SDD (MESH:C003361), PGE2 (MESH:D015232), chlorhexidine (MESH:D002710), nitric oxide (MESH:D009569), Resolvin E1 (MESH:C499823), doxycycline (MESH:D004318), alginate (MESH:D000464), LXA4 (MESH:C040527), pioglitazone (MESH:D000077205), lipid (MESH:D008055), belumosudil (MESH:C000718240), PLGA (MESH:D000077182), beta-glucan (MESH:D047071), lipoxins (MESH:D044045), BLAX4 (-), doxorubicin (MESH:D004317)
- **Species:** Lactococcus lactis (species) [taxon 1358], Pseudomonas aeruginosa (species) [taxon 287], Mus musculus (house mouse, species) [taxon 10090], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Levilactobacillus brevis (species) [taxon 1580], Lactiplantibacillus plantarum (species) [taxon 1590], Limosilactobacillus reuteri (species) [taxon 1598], Porphyromonas gingivalis (species) [taxon 837], Lactobacillus gasseri (species) [taxon 1596], Viruses (acellular root) [taxon 10239], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Leptospira sp. AB (species) [taxon 103236], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

73 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963321/full.md

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Source: https://tomesphere.com/paper/PMC12963321