Nonalcoholic fatty liver disease as an endogenous factor of dysbiosis in the structure of oral microbiome

Objective — to study the dysbiotic impairment on the example of some aggressive periodontopathogens in the oral microbiome of patients with NAFLD. 
Materials and methods. The study involved 126 patients with NAFLD diagnosis against the background of I — III degrees of obesity or overweight (the main group) and 20 practically healthy subjects with normal body weight without clinical disorders of the digestive system and signs of liver steatosis (control group). All patients underwent investigation of the intestinal microbiota composition at the level of the main phylotypes by identifying total bacterial DNA and DNA of Bacteroidetes, Firmicutes and Actinobacteria by quantitative PCR. The dental examination was carried out according to the standard methods with determination of the OHI‑S hygienic index and periodontal indices. The following physical saliva indicators were evaluated: the salivation rate of unstimulated mixed saliva, viscosity and pH. To determine the periodontopathogens levels, material was collected from the periodontal pockets using paper endodontic absorbers by the real‑time polymerase chain reaction (PCR) method (qRT‑PCR) using universal primers. Determination of the concentration of gingipain K in the oral fluid was carried out by the immunoenzymatic method using the set of reagents. 
Results. Analysis of the intestinal microbiome (IM) structure demonstrated the presence of a dysbiotic shift in NAFLD patients towards the predominance of the Firmicutes phylotype over Bacteroides (p < 0.01). The level of endotoxemia was significantly higher in patients of the main group (0.9 [0.6; 1.08], p = 0.000) in contrast to the control group (0.43 [0.12; 0.55], p = 0.000). Negative changes in the physical indicators of saliva/ oral fluid in patients of the main group were recorded, namely, a decrease in the rate of salivation and pH (0.26 ± 0.006; 6.46 ± 0.01, respectively) and an increase in viscosity (3.13 ± 0.05). The results’ difference between groups was significant (p = 0.000). The presence of a dysbiotic shift in the econiche‑gingival sulcus in patients of the main group with the prevalence of aggressive periodontopathogens of the first order — Porphyromonas gingivalis (5.49 [3.5; 6.37] LogGE/ mL) and Tannerella forsythia (5.09 [3.65; 6.45] LogGE/  mL) was revealed, which was also characterized by an increase in the level of endotoxin (33.5 [23.8; 52.3]) and gingipain (98.9 [84.2; 128.6]) in oral fluid. In 67.4 % of patients of the main group, periodontal disease of an inflammatory‑destructive nature — chronic periodontitis (CP) was detected. The level of quality of performing oral hygiene at home was unsatisfactory in patients of the main group and was, on average, 2.3 points according to the OHI–S index. 
Conclusions. The chronic inflammatory process is the basis of the pathogenesis of NAFLD and CP and has a comorbid nature, due to the mutual production of systemically active proinflammatory cytokines and endotoxin. The entry of periodontopathogens of the first order into the intestine biotope from the source of CP against the background of NAFLD and maintenance of a dysbiotic shift in it has isolated confirmation in experiments, but requires further, compatible, in‑depth scientific studies of dentistry and internal medicine.