Increasing evidence indicates that periodontitis affects non-alcoholic fatty liver disease (NAFLD). We examined the relationship between periodontal bacterial infection and clinical/biochemical parameters in 52 NAFLD patients. Anti-Aggregatibacter actinomycetemcomitans (Aa) antibody titers correlated positively with visceral fat, fasting plasma insulin, and HOMA-IR; and negatively with the liver/spleen ratio. C57BL/6J mice (8-weeks-old) were given Aa or saline (control) for 6 weeks, and were fed either normal chow (NCAa, NCco) or high-fat diet (HFAa and HFco). NCAa and HFAa mice presented impaired glucose tolerance and insulin resistance compared to control mice. HFAa mice showed higher hepatic steatosis than HFco animals. Liver microarray analysis revealed that 266 genes were differentially expressed between NCAa and NCco mice. Upregulated genes in Aa-administrated mice were enriched for glucagon signaling pathway, adipocytokine signaling pathway and insulin resistance. Consistently, plasma glucagon concentration was higher in NCAa mice. In addition, Akt phosphorylation was lower in the liver of NCAa/HFAa than in NCco/HFco mice. Based on 16S rRNA sequencing, Aa administration changed composition of the gut microbiota. Metagenome prediction in gut microbiota showed upregulation of fatty acid biosynthesis and downregulation of fatty acid degradation in Aa-administered mice. Thus, infection with Aa affects NAFLD by altering the gut microbiota and glucose metabolism.

Many risk factors related to the development of non-alcoholic fatty liver disease (NAFLD) have been proposed, including the most well-known of diabetes and obesity as well as periodontitis. As periodontal pathogenic bacteria produce endotoxins, periodontal treatment can result in endotoxemia. The aim of this study was to investigate the effects of intravenous, sonicated Porphyromonas gingivalis (Pg) injection on glucose/lipid metabolism, liver steatosis, and gut microbiota in mice. Endotoxemia was induced in C57BL/6J mice (8 weeks old) by intravenous injection of sonicated Pg; Pg was deactivated but its endotoxin remained. The mice were fed a high-fat diet and administered sonicated Pg (HFPg) or saline (HFco) injections for 12 weeks. Liver steatosis, glucose metabolism, and gene expression in the liver were evaluated. 16S rRNA gene sequencing with metagenome prediction was performed on the gut microbiota. Compared to HFco mice, HFPg mice exhibited impaired glucose tolerance and insulin resistance along with increased liver steatosis. Liver microarray analysis demonstrated that 1278 genes were differentially expressed between HFco and HFPg mice. Gene set enrichment analysis showed that fatty acid metabolism, hypoxia, and TNFα signaling via NFκB gene sets were enriched in HFPg mice. Although sonicated Pg did not directly reach the gut, it changed the gut microbiota and decreased bacterial diversity in HFPg mice. Metagenome prediction in the gut microbiota showed enriched citrate cycle and carbon fixation pathways in prokaryotes. Overall, intravenous injection of sonicated Pg caused impaired glucose tolerance, insulin resistance, and liver steatosis in mice fed high-fat diets. Thus, blood infusion of Pg contributes to NAFLD and alters the gut microbiota.

Periodontitis is a chronic inflammatory disease that affects the interface of teeth and surrounding tissues. Gingival crevicular fluid (GCF) is an exudate of the periodontal tissues and can be collected from the gap between the tooth and gum (gingival sulcus or periodontal pocket) with paper strips. Testing of GCF is a low‐cost and minimally invasive procedure. In a variety of diseases, microRNAs (miRNAs) in body fluids are implicated in pathogenesis, and are suggested as potential diagnostic biomarkers. Here, we profiled miRNAs in GCF (two chronic periodontitis, one aggressive periodontitis, and five healthy subjects) using miRCURY LNA™ Universal RT microRNA PCR System, which yielded quantitative measures of more than 600 miRNAs. Through this analysis, we found that miRNA profiles in GCF of periodontitis patients are distinct from those of healthy controls. We further selected 40 miRNAs and confirmed their differential expression patterns in different subjects (five chronic periodontitis, one aggressive periodontitis, and six healthy subjects) using a custom miRNA PCR panel. This is the first demonstration of miRNA profiling in GCF and its alteration in periodontitis. Our findings suggest that a subset of miRNAs in GCF holds potential as a biomarker for periodontitis.

Objectives Increasing evidence suggests that periodontitis can exacerbate diabetes, and gut bacterial dysbiosis appears to be linked with the diabetic condition. The present study examined the effects of oral administration of the periodontopathic bacterium, Porphyromonas gingivalis, on the gut microbiota and systemic conditions in streptozotocin‐induced diabetic mice. Materials and Methods Diabetes was induced by streptozotocin injection in C57BL/6J male mice (STZ). STZ and wild‐type (WT) mice were orally administered P. gingivalis (STZPg, WTPg) or saline (STZco, WTco). Feces were collected, and the gut microbiome was examined by 16S rRNA gene sequencing. The expression of genes related to inflammation, epithelial tight junctions, and glucose/fatty acid metabolism in the ileum or liver were examined by quantitative PCR. Results The relative abundance of several genera, including Brevibacterium, Corynebacterium, and Facklamia, was significantly increased in STZco mice compared to WTco mice. The relative abundances of Staphylococcus and Turicibacter in the gut microbiome were altered by oral administration of P. gingivalis in STZ mice. STZPg mice showed higher concentrations of fasting blood glucose and inflammatory genes levels in the ileum, compared to STZco mice. Conclusions Oral administration of P. gingivalis altered the gut microbiota and aggravated glycemic control in streptozotocin‐induced diabetic mice.