Experimental Inoculation of Aggregatibacter actinomycetemcomitans and Streptococcus gordonii and Its Impact on Alveolar Bone Loss and Oral and Gut Microbiomes.

Oral bacteria are implicated not only in oral diseases but also in gut dysbiosis and inflammatory conditions throughout the body. The periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) often occurs in complex oral biofilms with Streptococcus gordonii (Sg), and this interaction might influence the pathogenic potential of this pathogen. This study aims to assess the impact of oral inoculation with Aa, Sg, and their association (Aa+Sg) on alveolar bone loss, oral microbiome, and their potential effects on intestinal health in a murine model. Sg and/or Aa were orally administered to C57Bl/6 mice, three times per week, for 4 weeks. Aa was also injected into the gingiva three times during the initial experimental week. After 30 days, alveolar bone loss, expression of genes related to inflammation and mucosal permeability in the intestine, serum LPS levels, and the composition of oral and intestinal microbiomes were determined. Alveolar bone resorption was detected in Aa, Sg, and Aa+Sg groups, although Aa bone levels did not differ from that of the SHAM-inoculated group. Il-1ß expression was upregulated in the Aa group relative to the other infected groups, while Il-6 expression was downregulated in infected groups. Aa or Sg downregulated the expression of tight junction genes Cldn 1, Cldn 2, Ocdn, and Zo-1 whereas infection with Aa+Sg led to their upregulation, except for Cldn 1. Aa was detected in the oral biofilm of the Aa+Sg group but not in the gut. Infections altered oral and gut microbiomes. The oral biofilm of the Aa group showed increased abundance of Gammaproteobacteria, Enterobacterales, and Alloprevotella, while Sg administration enhanced the abundance of Alloprevotella and Rothia. The gut microbiome of infected groups showed reduced abundance of Erysipelotrichaceae. Infection with Aa or Sg disrupts both oral and gut microbiomes, impacting oral and gut homeostasis. While the combination of Aa with Sg promotes Aa survival in the oral cavity, it mitigates the adverse effects of Aa in the gut, suggesting a beneficial role of Sg associations in gut health.

Lactobacillus acidophilus LA-5 Ameliorates Inflammation and Alveolar Bone Loss Promoted by A. actinomycetemcomitans and S. gordonii in Mice and Impacts Oral and Gut Microbiomes.

The benefits of probiotics on dysbiotic microbiomes and inflammation are dependent on the tested strain, host factors, and the resident microbiome. There is limited knowledge on the effects of probiotics in A. actinomycetemcomitans-associated periodontitis. Thus, Lactobacillus acidophilus LA5 (LA5) was orally inoculated for 30 days in C57Bl/6 mice infected with A. actinomycetemcomitans JP2 (Aa) and S. gordonii (Sg). Alveolar bone loss, gingival gene expression, and oral and gut microbiomes were determined. LA5 controlled bone loss in Aa+Sg-infected mice, downregulated the expression of Il-1ß and upregulated Il-10 in gingival tissues, and altered the oral and gut microbiomes. LA5 increased the diversity of the oral microbiome of Aa+Sg infected mice, and Aa+Sg and Aa+Sg+LA5 oral or gut microbiomes clustered apart. LA5 induced shifts in Aa+Sg infected mice by increasing the abundance of Muribaculaceae and decreasing Bifidobacteriaceae in the oral cavity and increasing the abundance of Verrucomicrobiae and Eggerthellales in the gut. In conclusion, LA5 oral administration controls experimental Aa-associated periodontitis by altering inflammatory gene expression and the oral and gut microbiomes.

Systemic circulating inflammatory burden and periodontitis in adolescents.

OBJECTIVES: To analyze the association between systemic inflammatory burden of cardiovascular disease (CVD) risk and periodontitis in adolescents, including mediating pathways triggered by their common risk factors. MATERIALS AND METHODS: Using a population-based sample study (n = 405) of Brazilian adolescents (17-18 years old), direct and mediation pathways triggered by "Socioeconomic Status," "Adiposity," Smoking, and "Blood Pressure" were modelled for the association between the "Systemic Circulating Inflammatory Burden of CVD Risk" (IL-1ß, IL-6, IL-8, TNF-α) and the "Initial Periodontitis" (bleeding on probing (BoP), probing depth (PD) ≥ 4 mm, clinical attachment loss (CAL) ≥ 4 mm), both as continuous latent variables, using structural equation modeling. Sensitivity analysis was performed for the outcomes "Gingivitis" (visible plaque; BoP); "Moderate Periodontitis" (PD ≥ 5 mm and CAL ≥ 5 mm) and periodontitis (CDC-AAP case definition). RESULTS: Higher "Systemic Circulating Inflammatory Burden of CVD Risk" was directly associated with higher "Initial Periodontitis" (standardized coefficient [SC] = 0.178, P value < 0.001). Lower "Socioeconomic Status" (SC = - 0.022, P value = 0.015) and Smoking (SC = 0.030, P value = 0.021) triggered the "Initial Periodontitis", mediated by "Systemic Circulating Inflammatory Burden of CVD Risk". Sensitivity analysis showed a dose-response relationship between "Systemic Circulating Inflammatory Burden of CVD Risk" and "Moderate Periodontitis" (SC = 0.323, P value = 0.021). CONCLUSIONS: "Systemic Circulating Inflammatory Burden of CVD Risk" appeared as an underlying mechanism of early periodontal breakdown in adolescents, also triggered by social vulnerability and smoking. CLINICAL RELEVANCE: The association between periodontitis and CVD in adulthood seems to establish much earlier in life than had been previously studied, giving impetus to preventive approaches focused on their common risk factors.