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. 2024 Jan 6;10(2):e24089.
doi: 10.1016/j.heliyon.2024.e24089. eCollection 2024 Jan 30.

Association between dysbiotic perio-pathogens and inflammatory initiators and mediators in COVID-19 patients with diabetes

Endang W Bachtiar  1   2 , Boy M Bachtiar  1   2 , Ardiana Kusumaningrum  3 , Hari Sunarto  4   5 , Yuniarti Soeroso  4 , Benso Sulijaya  4 , Citra Fragrantia Theodorea  1   2 , Irandi Putra Pratomo  6   7   8 , Yudhistira  9 , Defi Efendi  10 , Efa Apriyanti  11 , Shahida Mohd Said  12
Affiliations

Association between dysbiotic perio-pathogens and inflammatory initiators and mediators in COVID-19 patients with diabetes

Endang W Bachtiar et al. Heliyon. .

Abstract

It has been suggested that a corona virus infection is linked to chronic periodontitis (COVID-19). Our objectives were to look at the expression of angiotensin-converting enzyme-2 (ACE2) in periodontal compartments containing periodontal infections to determine if ACE2 is directly or indirectly responsible for the inflammation in periodontal tissues getting worse. In this study, six non-COVID-19 periodontitis patients without diabetes served as controls, and 23 hospitalized periodontitis patients were admitted with PCR-confirmed COVID-19 with diabetes mellitus (Group 1/G1, n = 10), and without diabetes (Group 2/G2, n = 13). We evaluated the mRNA expression of ACE2, IL-6, IL-8, complement C3, and LL-37, as well as the relative proportion of Porphyromonas gingivalis, Fusobacterium nucleatum, and Veillonella parvula to represent the dysbiosis condition in periodontal microenvironment using subgingival plaque and gingival crevicular fluids (GCF) samples and quantitative real time PCR (qPCR). Every analysis was done to ascertain how they related to one another. The area under the curve (AUC) and receiver operating characteristic (ROC) curve were used to determine the sensitivity and specificity of inflammatory indicators. All the grouped patients had ACE2 detected, according to our findings, but only the G1 patients had a positive correlation (p < 0.05) between ACE2 expression and the inflammatory markers. The combination of IL-6 and C3 mRNAs was found to be 0.78 and 0.55 for the G1 group and the G2 group, respectively, based on the ROC and AUC values. According to our research, the relationship between complement C3 and IL-6 may be able to predict the degree of periodontal inflammation in COVID-19 patients who also have diabetes.

Keywords: ACE2; Corona virus; Diabetes; Dysbiosis; Gingival crevicular fluid; Inflammation; Periodontitis; mRNA expression.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
ACE2 expression, the proportion of P. gingivalis (Pg), Fusobacterium nucleatum (Fn), Veillonella parvula (Vp), and their relationship in different patient groups of COVID-19. The transcription level of ACE2 mRNA was higher in COVID-19 patients with (G1) diabetes than those without (G2) diabetes, but the reverse was found in tongue surface/TS (A). The proportion of Pg was found to be the lowest compared to the other two species (Fn and Vp). However, the relative abundance of Pg was not significant in either G1 or G2 patient group (B). In both groups, the correlations were significant moderate (E and H) and strongly positive, C, D, F, and G). All data are expressed as mean ± SE. * significant difference in the gene expression within the group (G1 and G2). ** significant difference of the gene expression between GCF and TS or between Pg and Fn. ns = not a significant difference. # significant difference in the bacterial abundance Vp and Pg and Fn. The inserts denote the melting curve of qPCR in GCF (left) and TS (right) samples.
Fig. 2
Fig. 2
Transcription levels of Il-6 and IL-8 genes and the correlation between the mRNA expression of ACE2 or the proportion of P. gingivalis and IL-6/IL8 in gingival crevicular fluids (CGF) of COVID-19 patients with (G1) and without (G2) diabetes. In general, mRNA expression of Il-6 and Il-8 was higher in G1 than in G2 group. However, in either group, the transcription level of IL-6 was higher than IL-8 (A). This study shows, that in the G1 group, ACE2 transcription level and P. gingivalis abundance show a strong positive correlation with the transcription levels of IL-6 (B and D). In G2 group, a negative correlation was observed between ACE2 and Il-6 transcripts (C), whereas a strong positive relationship was observed between P. gingivalis abundance and the transcription level of IL-6 (E). *P < 0.05 within groups, **P < 0.05 between group.
Fig. 3
Fig. 3
Transcription levels of C3 and LL-37 genes and the correlation between the mRNA expression of ACE2 or the proportion of P. gingivalis and C3/LL-37 in gingival crevicular fluids (CGF) of COVID-19 patients with (G1) and without (G2) diabetes. In general, mRNA expression of C3 and LL-37 was higher in G1 than in G2 group. However, in either group, the transcription level of C3 was higher than LL-37 (A). This study indicates, that in G1 and G2 groups, the transcription ACE2 mRNA and P. gingivalis abundance show a strong positive correlation with the transcription levels of C3 mRNA (B, C, D, and E). For LL-37, its associations with ACE2 mRNA or P. gingivalis abundance were strongly positive in G1 (F and H). In G2, the correlation was found to be negative, not significant with ACE2, but strong positive with P. gingivalis abundance (G and I). *P < 0.05 within groups, **P < 0.05 between groups.
Fig. 4
Fig. 4
Receiver operating characteristic curve (ROC) showing the plot and the best cut-off point of the relationship between IL-6 and C3. The combination of IL-6 and C3 mRNA expression could discriminate the aggressive of periodontitis in COVID-19 patients with diabetes (A) (area under curve/AUC, 0.78; P = 0.04) and without diabetes (B) (area under curve/AUC, 0.5; P = 0.7).
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