Search

Aim: In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. Methodology: Sixteen 7‐week‐old male apolipoprotein E knockout (apoE−/−) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first‐ and second‐maxillary molars with bacterium‐containing cotton balls. Apical lesions were evaluated by micro‐CT. Histological evaluations of NAFLD were performed using second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography–mass spectrometry (LC–MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. Results: Micro‐CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p <.05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D‐galactosamine, were enriched and that 16‐hydroxyhexadecanoic acid and 3‐methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin‐1 expression in the CAP group. Conclusion: This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism. [ABSTRACT FROM AUTHOR]

Aim: There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis. Methodology: Twenty‐four 5‐week‐old lipoprotein E knockout (apoE−/−) mice were randomly divided into four groups: the CAP group, Con group, Co‐CAP (cohoused with CAP) and Co‐Con (cohoused with Con) group. In the CAP group, sterile cotton wool containing P. gingivalis was placed into the exposed pulp chamber, followed by coronal resin‐based composite restoration of the bilateral maxillary first and second molars. In the Con group, a sham operation was performed. Biweekly, mice in the CAP group were anaesthetised to check the sealing of coronal access. Meanwhile, the animals in the Con group were anaesthetised. The cohousing approach was used to introduce gut microbiota from the CAP and Con groups into the Co‐CAP and Co‐Con groups, respectively. Alterations in the abundance and diversity of the gut microbiota were detected using 16S rRNA sequencing, Oil‐red O staining was used to demonstrate the extent of lesions, and serum levels of trimethylamine N‐oxide (TMAO), and immunohistochemistry of flavin‐containing monooxygenase 3 (FMO3) in liver were used to assess TMAO‐related metabolic alterations. Results: Alterations of alpha and beta diversity were shown both in the CAP and the Co‐CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co‐CAP groups (p <.05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p <.05), which were positively correlated with serum TMAO levels (p <.05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co‐occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p <.05). Conclusion: Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of chronic apical periodontitis (CAP) on atherosclerosis and gut microbiota by establishing a Porphyromonas gingivalis (P. gingivalis)‐induced CAP in an apolipoprotein E‐deficient (apoE−/−) mice model. Methodology: Twenty‐eight male apoE−/− mice were divided into two groups with 14 in each: CAP group and control group. In the CAP group, sterile cotton wool containing 108 colony‐forming units of P. gingivalis was placed into the pulp chamber after pulp exposure followed by coronal resin filling in bilateral maxillary first and second molars. The mice were fed with a chow diet to induce atherosclerosis. Animals were euthanized 16 weeks after the operation, and the periapical lesions of bilateral maxillary first and second molars were assessed by micro‐CT. After collection of aortic arches, atherosclerotic lesions were measured by Oil Red O staining. Serum levels of high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), and triglycerides (TG) were measured. Stools were collected to detect alterations in gut microbiota by 16S rRNA gene sequencing. Independent samples t‐test was used to calculate the difference between the two groups. Results: CAP was observed in 98.2% of molars. A significant increase in atherosclerotic plaque formation in the aortic arches was found in the CAP groups (CAP: 2.001% ± 0.27%, control: 0.927% ± 0.22%, p =.005). No significant difference was observed between sevum level of HDL‐C (CAP: 2.295 ± 0.31 mmol/L, Control: 3.037 ± 0.55 mmol/L, p =.264) or LDL‐C (CAP: 17.066 ± 3.95 mmol/L, Control: 10.948 ± 1.69 mmol/L, p =.177) in CAP group and Control group. There were no significant differences in TG (CAP: 1.076 ± 0.08 mmol/L, control: 1.034 ± 0.13 mmol/L, p =.794) or TC (CAP: 6.372 ± 0.98 mmol/L, control: 6.679 ± 0.75 mmol/L, p =.72) levels between the two groups (p >.05). The alpha diversity was elevated in the CAP group. In terms of beta diversity, the CAP and control groups were clearly distinguished by the microbial community. Conclusion: In a mouse experimental model, pulp infection with P. gingivalis ‐induced CAP, thus aggravating the development of atherosclerosis. Meanwhile, CAP increased alpha diversity and altered the beta diversity of the gut microbiota. [ABSTRACT FROM AUTHOR]