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.

Stroke is associated with multiple forms of disability, including dysphagia. Post-stroke dysphagia increases the risks of pneumonia and mortality and often results in cessation of oral feeding. However, appropriate rehabilitation methods can eventually lead to resumption of oral food intake. This study tried to clarify that re-initiating oral food intake could modify the composition of oral/gut microbial communities in patients with dysphagia. From 78 patients with sub-acute stage of stroke, 11 complete tube feeding subjects without taking antibiotics were enrolled and received rehabilitation for re-initiation of oral food intake, and 8 subjects were brought back to complete oral feeding. Oral and gut microbiota community profiles were evaluated using 16S rRNA sequencing of the saliva and feces samples before and after re-initiation of oral food intake in patients recovering from enteral nutrition under the same nutrient condition. Standard nutrition in the hospital was 1,840 kcal, including protein = 75 g, fat = 45 g, and carbohydrates = 280 g both for tube and oral feeding subjects. Oral food intake increased oral and gut microbiome diversity and altered the composition of the microbiome. Oral and gut microbiome compositions were drastically different; however, the abundance of family Carnobacteriaceae and genus Granulicatella was increased in both the oral and gut microbiome after re-initiation of oral food intake. Although oral microbiota showed more significant changes than the gut microbiota, metagenome prediction revealed the presence of more differentially enriched pathways in the gut. In addition, simpler co-occurrence networks of oral and gut microbiomes, indicating improved dysbiosis of the microbiome, were observed during oral feeding as compared to that during tube feeding. Oral food intake affects oral and gut microbiomes in patients recovering from enteral nutrition. Rehabilitation for dysphagia can modify systemic health by increasing the diversity and altering the composition and co-occurrence network structure of oral and gut microbial communities.

Objective: Growing evidence indicates an association between periodontitis and delivery outcome; however, the mechanism is unclear. This study aimed to investigate the influence of Porphyromonas gingivalis (Pg) infection on delivery outcome in mice. Materials and methods: Bacteremia was induced in pregnant Slc:ICR mice (8 weeks old) by intravenous injection of Pg. Mice were randomly divided into a control group (CO), and those receiving Pg injection at gestational day 1 (GD1), gestational day 15 (GD15) or every day (ED). Delivery outcome, Pg infection, and gene expression in the placenta and umbilical cord were evaluated. Results: Birth weight was lower in the ED and GD15 groups than in the CO group. A remarkable increase in anti-Pg IgG antibody was observed in the ED and GD1 groups, although Pg was not detected in the placenta or umbilical cord. mRNA expression of Tnfα and Il6 in the placenta, and Hif1α in the umbilical cord, was significantly increased in the ED group. Microarray analysis of the umbilical cord revealed increased expression of several genes including Orm1, Mgl2, Rps6ka3 and Trim15 in the ED group. Conclusions: Pg infection during the third trimester caused low birth weight and inflammation in the placenta and umbilical cord.