**4. Discussion**

Despite existing literature pointing to a potential role of lipopolysaccharide in modulating allergic reactions, it remains a relatively underresearched subject matter. Notably, the majority of existing research has only investigated the interactions between periodontitis and clinical symptoms of allergies [24]. In this research, we had observed a direct correlation between lipopolysaccharide of *Porphyromonas gingivalis* with atopic inflammatory markers.

Lipopolysaccharide is a gram-negative endotoxin, ubiquitous in the environment and can therefore exacerbate allergic responses [25]. Existing literature has demonstrated the pathogenic role of *Porphyromonas gingivalis* dental biofilm to stimulate lipopolysaccharide-driven inflammatory responses [26], and therefore, lack of dental plaque and calculus in supra-gingival surface, sub-gingival surface, as well as human epithelial cell rests of Malassez account for the lack of response to lipopolysaccharide to induce host inflammatory responses [27].

As a unique endotoxin, lipopolysaccharide-driven inflammatory responses can induce a more pronounced pro-inflammatory cytokine response [28]. At very low concentration, lipopolysaccharide may induce atopic inflammatory responses by Th-1 shifting into Th-2, which is more potent to stimulate antibodies production [29]. Lipopolysaccharide binds to Toll-like receptor (TLR) 4 and greatly enhances the response of TLR4-transfected cells [30]. Thus, damage from lipopolysaccharide extends beyond the exhaustion of host innate immunity [31].

Lipopolysaccharide activates macrophage via the TLR4/NF-κB pathway [32]. In turn, TLR4 activation increases SOCS3 mRNA expression [33]. Since SOCS3 is an inducible endogenous negative regulator of JAK/STAT pathway [34], therefore administration of lipopolysaccharide in a model of experimental periodontal disease will be correlated with dynamics of the atopic inflammatory reaction [35]. Meanwhile, given the unique lipopolysaccharide-induced atopic inflammatory responses and lipopolysaccharide-triggered mast cell derived, we can predict that lipopolysaccharide of this periodontal pathogen may stimulate the level of circulatory Ig-E and Ig-G4, even in the healthy populations [36, 37].

In line with the hypothesis, our present study confirms the existence of a significant correlation between salivary lipopolysaccharide of *Porphyromonas gingivalis* with the circulatory Ig-E and Ig-G4 in periodontally healthy children with house dust mite allergy. Importantly, this association remained even after adjusting for baseline and clinical parameters, suggesting an independent association between salivary lipopolysaccharide and allergic biomarkers.

This study had several limitations. Firstly, this study had small sample size, limiting the generalizability of the results. Perhaps more observations with longer periods would have been statistically significant with a larger sample size. Secondly, the cross-sectional approach of this current study cannot draw any

**39**

*Correlation between Salivary Lipopolysaccharide of Porphyromonas gingivalis with Circulatory…*

conclusions concerning direct relationships. Given the correlational nature of the analysis, we cannot clarify whether salivary lipopolysaccharide of *Porphyromonas gingivalis* is the direct cause of high circulatory Ig-E and Ig-G4 in periodontally healthy children with house dust mite allergy. Lastly, this study did not assess the levels of house dust mite-specific serum Ig-E and the effect of increasing Ig-E level with the occurrence of allergic manifestation. Indeed, studies have recognized that evaluating an allergic manifestation and quantifying the levels of house dust mite-specific serum Ig-E are critical requisites when trying to establish an association with salivary lipopolysaccharide of *Porphyromonas gingivalis*. Nevertheless, this was beyond the scope of the present study, which aimed to investigate the correlation between salivary lipopolysaccharide and atopic

In conclusion, salivary lipopolysaccharide of *Porphyromonas gingivalis* might serve as a predictor for circulatory Ig-E and Ig-G4 in periodontally healthy children with house dust mite allergy. These data might guide future studies on the actual role of these periodontal pathogens with the progression and sensitization of allergic diseases and help to establish a more effective treatment for child allergies. With increasingly more studies indicating the association of *Porphyromonas gingivalis* colonization and its lipopolysaccharide in an allergic child in the future, clinicians should be more aware about these periodontal pathogens in children's saliva and gum tissue. Despite a rare progression into a localized aggressive periodontitis, chronic gingivitis should be treated well in children, since its lipopolysaccharide

The authors thank all subjects and their parents for participating in this study. The authors also thank laboratory assistants and pediatric dentistry nurses at Dr. Soetomo General Hospital (Surabaya, Indonesia) for their technical support in this

Most of the experimental data acquired/analyzed during this study have been included in this published version. Information on rest of the data is available from

*DOI: http://dx.doi.org/10.5772/intechopen.81113*

may be linked with allergic diseases in the future.

All authors declare no conflict of interests in this study.

inflammatory markers.

**Acknowledgements**

**Conflict of interests**

**Consent for publication**

Not applicable.

**Availability of data and materials**

the corresponding author on reasonable request.

study.

**5. Conclusion**

*Correlation between Salivary Lipopolysaccharide of Porphyromonas gingivalis with Circulatory… DOI: http://dx.doi.org/10.5772/intechopen.81113*

conclusions concerning direct relationships. Given the correlational nature of the analysis, we cannot clarify whether salivary lipopolysaccharide of *Porphyromonas gingivalis* is the direct cause of high circulatory Ig-E and Ig-G4 in periodontally healthy children with house dust mite allergy. Lastly, this study did not assess the levels of house dust mite-specific serum Ig-E and the effect of increasing Ig-E level with the occurrence of allergic manifestation. Indeed, studies have recognized that evaluating an allergic manifestation and quantifying the levels of house dust mite-specific serum Ig-E are critical requisites when trying to establish an association with salivary lipopolysaccharide of *Porphyromonas gingivalis*. Nevertheless, this was beyond the scope of the present study, which aimed to investigate the correlation between salivary lipopolysaccharide and atopic inflammatory markers.
