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Review
. 2025 Apr 30:15:1556688.
doi: 10.3389/fcimb.2025.1556688. eCollection 2025.

Innovative strategies targeting oral microbial dysbiosis: unraveling mechanisms and advancing therapies for periodontitis

Yang Li  1   2 , Xinyu He  1 , Guocheng Luo  1 , Juanjuan Zhao  3 , Guohui Bai  2 , Delin Xu  1
Affiliations
Review

Innovative strategies targeting oral microbial dysbiosis: unraveling mechanisms and advancing therapies for periodontitis

Yang Li et al. Front Cell Infect Microbiol. .

Abstract

Periodontitis, a prevalent inflammatory oral disease, is intricately linked to disruptions in the oral microbiome, a state known as microbial dysbiosis. This review explores the pivotal roles of key pathogens, including Porphyromonas gingivalis and Tannerella forsythia, in driving periodontitis and examines the underlying molecular mechanisms that disrupt microbial homeostasis. We discuss how interactions among bacterial species affect the oral ecosystem's balance and how microbial metabolites influence the host immune responses, contributing to disease progression. Leveraging these insights, we propose cutting-edge therapeutic approaches aimed at restoring microbial equilibrium. These include personalized pharmacological interventions tailored to individual microbiome profiles and innovative microbiome-targeted strategies such as probiotic formulations and bacteriophage therapy. By precisely modulating microbial communities, these strategies hold promise for enhancing treatment efficacy, preventing disease recurrence, and mitigating issues like antimicrobial resistance. Overall, this review paves the way for novel prevention and management techniques in periodontitis, offering significant improvements in oral health outcomes for patients.

Keywords: mechanistic insights; microbial dysbiosis; oral microbiome; periodontitis; therapeutic strategies inflammatory response.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
P. gingivalis: a veritable arsenal of virulence factors fueling periodontal destruction. TLRs, Toll-like receptors; LPS, Lipolyaccharide; OMVs, Outer membrane vesicles; HGFs, Human gingival fibroblasts; MMP-3, Matrix metalloproteinase-3.
Figure 2
Figure 2
T. forsythia’s multifaceted arsenal: fueling the flames of periodontal inflammation. OMVs, Outer membrane vesicles; TLR2, Toll-like receptor 2; tmTNF-α, The membrane-bound form of TNF-α; MMPs, Matrix metalloproteinases.
Figure 3
Figure 3
A. actinomycetemcomitans’s multifaceted virulence factors driving periodontal pathogenesis. LtxA, Leukotoxin A; CDTs, Cytotoxic distending toxins; MMPs, Matrix metalloproteinases; MPO, Myeloperoxidase; Les, Lysosomal enzymes; OmpA, Outer membrane protein A.
Figure 4
Figure 4
T. denticola’s multifaceted mechanisms fueling periodontal pathogenesis. MSP, major surface protein; PIP, Phosphoinositide processing; MMP-2, Metalloproteinase-2; HSP70, Heat shock protein 70.
Figure 5
Figure 5
P. intermedia’s multifarious strategies fueling periodontal inflammation and destruction. Eh, REDOX potential; LPS, Lipopolysaccharide.
Figure 6
Figure 6
F. nucleatum’s multifaceted strategies fueling the vicious cycle of periodontal disease. PEBP1, Cytoplasmic protein phosphatidylethanolamine-binding protein 1.
Figure 7
Figure 7
Vicious cycles of periodontal pathogenesis: microbial interaction, host immunity and bacterial virulence.
See this image and copyright information in PMC

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