# Oral Microbiome and Host Health: Review on Current Advances in Genome-Wide Analysis
## 9 Oral Disease and Systemic Disease
### Non-Communicable Diseases
#### 9.1.2 Diabetes Mellitus  
Periodontitis and DM are representative chronic and high-prevalence diseases in the dental and medical fields, respectively [121]. DM is a metabolic disorder characterized by prolonged high blood glucose level, which could lead to systemic complications such as CVD and circulatory problems, including peripheral vascular disease. In 2017, the International Diabetic Federation listed periodontitis as a risk factor of DM [122]. The majority of studies on DM and periodontitis have focused on type 2 DM [123; 124], and the relationship of type 1 DM with periodontal disease in young patients [125]. The association between these two diseases has been studied for many years, and it is believed that the two have bidirectional links, implying that DM is a risk factor of periodontitis and periodontitis adversely affects glycemic control [126; 127; 128]. It has been known that the oral microbiota plays an important role in the relationship between DM and periodontitis because it affects blood glycemic control [129]. Disturbances in the oral microbiome are considered to be factors of periodontal disease initiation and progression and DM [130], and several studies have been conducted to understand this cause-and-effect relationship (Table 3). [PERSON] et al. showed the alteration in the composition of oral microbiomes across glycemic status as well as different stages of periodontal disease using 16S rDNA sequencing in dental plaque samples from South Africa [91]. Additionally, other studies with high-throughput metagenomic sequencing (16S rDNA or rRNA) of oral microbiomes also demonstrated the role of the oral microbiome in the development of DM [131; 132; 133]. Recently, [PERSON] et al. reported that the treatment of periodontitis could reduce inflammation in DM patients, indicating that diabetes and periodontitis together increase systemic inflammation [134]. Similarly, a systematic review has proven that periodontal treatment, such as scaling and root planing, improves the glycemic control in DM [135]. In contrast, some reports raised the question about the effect periodontal treatment has on the glycemic control of DM patients [136; 137], and showed there is no difference in oral microbiota between those with and those without DM [138; 139]. These contrasting results might be due to the different types of detection methods, sampling conditions, and analysis techniques used; therefore, a comprehensive understanding with more controlled procedures and analyses would be necessary to explain the link between oral microbiome and DM.  
\begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline
**Mechanism** & **Organism** & **Result** & **Reference** \\ \hline \multirow{8}{*}{Toll-like receptors-mediated mechanism} & & A.a. infection of apolipoprotein E-deficient mice resulted in increased expression in the aorta of TLR2 and TLR4 & [111] \\ \cline{2-4}  & & P.g. stimulates the expression of TLR2 and TLR & \\ \cline{1-1} \cline{2-4}  & & P.g. stimulates the expression of TLR2 and TLR & \\ \cline{1-1} \cline{2-4}  & & 4 on the surface of endothelial cells. Endothelial cells incubated with P. g. LPS expressed ICAM-1 and VCAM-1 and antibodies against TLR2 & [116; 117] \\ \cline{1-1} \cline{2-4}  & & P.g. accelerates the atherosclerosis & \\ \cline{1-1} \cline{2-4}  & & apolipoprotein E-null mice & [118; 119; 120] \\ \hline \end{tabular}
\end{table}
Table 2: _Cont._  
\begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline
**Organism** & **Result** & **Reference** \\ \hline \multirow{8}{*}{P.g.} & P.g. triggers periodontal tissue destruction and increases insulin resistance & [140; 141] \\ \cline{2-4}  & P.g. with type II fimbrae is a critical infectious factor in the deterioration of periodontitis with DM & [142] \\ \cline{1-1} \cline{2-4}  & P.g. is involved with insulin resistance in DM & [143; 144; 145] \\ \hline \end{tabular}
\end{table}
Table 3: Oral Microbiome’s Relationship with DM.