Ligature Induced Periodontitis In Rats Causes Gut Dysbiosis Leading To Hepatic Injury Through SCD1/AMPK Signalling Pathway

Backgrounds: Chronic periodontitis（CP）is a common chronic non-specific bacterial infectious disease,characterized by gingival inflammation,periodontal pocket formation,attachment loss and alveolar bone damage defect,and eventually leads to tooth loss.Long-term persistent inflammatory damage allows the gradual spread of microorganisms and inflammatory mediators to the system.Previous studies have demonstrated that CP is closely related to the occurrence and development of various systemic diseases such as obesity,diabetes,and respiratory system diseases,and digestive system diseases,especially the effect on liver tissue.The relationship between intestinal flora and diseases has been a research hotspot in recent years.The balance of intestinal flora is involved in maintaining body health.Meanwhile,previous studies have shown that the disturbance of intestinal flora is closely related to the occurrence and development of systemic diseases.In this study,we successfully constructed a rat CP model through dental silk ligation,and the corresponding inflammatory reactions and fatty lesions were observed in the liver.Objectivs: To explore the intrinsic link between chronic periodontitis and liver injury,to provide a theoretical basis for the impact of chronic periodontitis on systemic diseases,and to explain the underlying molecular mechanisms.Methods: Sprague-Dawley rats（n = 6）underwent tooth ligation at the bilateral first molars with silk thread to induce CP and were sacrificed 8 weeks later and compared to non-ligated rats（n = 6）.RNA sequencing and 16 S r RNA analysis were performed to determine the molecular mechanisms of CP involved in inducing liver disease.Alveolar bone loss,liver enzymes,mandible and liver histopathology,and inflammatory responses were compared between groups.Results: RNA sequencing of liver tissue showed that the expression of SCD1 increased significantly in CP rats compared to controls.KEGG enrichment analysis showed that the AMPK signalling pathway may be involved in liver steatosis.The intestinal flora of faecal samples of rats were analysed by 16 S r RNA sequencing,and the results indicated that the intestinal flora of the CP group was evidently imbalanced.The expression levels of tight junction proteins（ZO-1,occludin,and claudin-1）were significantly reduced in CP rats.Meanwhile,increases in serum IL-1β and lipopolysaccharide in CP rats reflected a systemic inflammatory response.Conclution: CP may be involved in the occurrence and development of hepatic injury and liver steatosis,and its mechanism may be related to the oral-gut-liver axis and SCD1/AMPK signal activation in the liver.