Project description:The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Thus, the systemic effects of small differences in the oral microbiota are unclear. In this study, we explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects by analyzing the hepatic gene expression and serum metabolomic profiles. The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Samples were collected five weeks after administration. Gut microbial communities were analyzed by 16S ribosomal RNA gene sequencing. Hepatic gene expression profiles were analyzed using a DNA microarray and quantitative polymerase chain reaction. Serum metabolites were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The gut microbial composition at the genus level was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of Neat1, Mt1, Mt2, and Spindlin1, which are involved in lipid and glucose metabolism. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with Bifidobacterium, Atomobium, Campylobacter, and Haemophilus, which are characteristic taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.
Project description:This study compared the subgingival microbiota of subjects with periodontitis to those with periodontal health using the Human Oral Microbe Identification Microarray (HOMIM).
Project description:The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. Thus, the purpose of the present investigation was to compare metaproteomic profiles of saliva in oral health and disease. Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. Samples were analyzed by means of shotgun proteomics. 4161 different proteins were recorded out of which 1946 and 2090 were of bacterial and human origin respectively. The human proteomic profile displayed significant overexpression of the complement system and inflammatory mediators in periodontitis and dental caries. Bacterial proteomic profiles and functional annotation were very similar in health and disease. Data revealed multiple potential salivary proteomic biomarkers of oral disease. In addition, comparable bacterial functional profiles were observed in periodontitis, dental caries and oral health, which suggest that the salivary microbiota predominantly thrives in a planktonic state expressing no characteristic disease-associated metabolic activity. Future large-scale longitudinal studies are warranted to reveal the full potential of proteomic analysis of saliva as a biomarker of oral health and disease.
Project description:The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. Thus, the purpose of the present investigation was to compare metaproteomic profiles of saliva in oral health and disease. Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. Samples were analyzed by means of shotgun proteomics. 4161 different proteins were recorded out of which 1946 and 2090 were of bacterial and human origin respectively. The human proteomic profile displayed significant overexpression of the complement system and inflammatory mediators in periodontitis and dental caries. Bacterial proteomic profiles and functional annotation were very similar in health and disease. Data revealed multiple potential salivary proteomic biomarkers of oral disease. In addition, comparable bacterial functional profiles were observed in periodontitis, dental caries and oral health, which suggest that the salivary microbiota predominantly thrives in a planktonic state expressing no characteristic disease-associated metabolic activity. Future large-scale longitudinal studies are warranted to reveal the full potential of proteomic analysis of saliva as a biomarker of oral health and disease.
Project description:Animal model implicates microbiota-triggered oral mucosal Th17 cells as drivers of local immunopathology and therapeutic targets in periodontitis.
Project description:The oral mucosa remains an understudied barrier tissue rich in exposure to antigens, commensals and pathogens. Moreover, it is the tissue where one of the most prevalent human microbe-triggered inflammatory diseases, periodontitis, occurs. To understand this complex environment at the cellular level, we assemble herein a human single-cell transcriptome atlas of oral mucosal tissues in health and periodontitis. Our work reveals transcriptional diversity of stromal and immune cell populations, predicts intercellular communication and uncovers an altered immune responsiveness of stromal cells participating in tissue homeostasis and disease at the gingival mucosa. In health, we define unique populations of CXCL1,2,8- expressing epithelial cells and fibroblasts mediating immune homeostasis primarily through the recruitment of neutrophils. In disease, we further observe stromal, particularly fibroblast hyper-responsiveness linked to recruitment of leukocytes and neutrophil populations. Our work suggests a stromal-neutrophil axis as a key regulator of mucosal immunity. Pursuant to these findings, most Mendelian forms of periodontitis were shown to be linked to genetic mutations in neutrophil-expressed genes. Moreover, we document previously unappreciated expression of known pattern- and damage- recognition receptors on stromal cell populations in the setting of periodontitis, suggesting avenues for triggering of stromal responsiveness. This comprehensive atlas offers an important reference for in-depth understanding of oral mucosal homeostasis and inflammation and reveals unique stromal–immune interactions implicated in tissue immunity.