Project description:Plasminogen (Plg), the zymogen precursor of the serine protease plasmin, is synthesized by the liver and is present in high concentration in the circulation and in interstitial fluids to provide focal proteolysis, after being converted to plasmin by urokinase or tissue plasminogen activator. Homozygous or compound heterozygous mutations in the human Plg gene (PLG) typically lead to severe mucosal disease involvement suggesting, a critical role for this gene/pathway in mucosal immunity. Indeed, such patients present with deposition of fibrin at various mucosal sites leading to ocular disease (conjunctivitis), oral mucosal disease (ligneous periodontitis), lung, vaginal and gastrointestinal tract involvement. In the oral mucosa, local deposition of fibrin is hypothesized to lead to severe soft tissue and bone destruction around teeth and often loss of the entire dentition in adolescence. Mucosal inflammation in areas surrounding the dentition and destruction of underlying bone are also the hallmarks of the common human oral mucosal disease, periodontitis. Plg-deficient mice phenocopy the human disease and we aim to use this animal model to understand the mechanism underlying fibrin-mediated periodontal immunopathology in vivo. Herein, we analyse the transcriptome of gingival tissues extracted from Plg-deficient mice in comparison to their wild-type littermates at 12 weeks of age.
Project description:Background: Hypertension is one of the most common metabolic diseases in the elderly and its pathogenesis is associated with microbiota dysbiosis. Recent evidence suggests that oral microbiota dysbiosis is also an important factor in the development of hypertension. However, the relationship between hypertension and oral flora in the elderly has not been adequately investigated. Objective: The aim of this cross-sectional study was to investigate the structure of the oral microbiota and its correlation with hypertension in elderly hypertensive patients. To provide new ideas for the prevention and treatment of hypertension. Methods: 206 subjects aged 60 ~ 89 years were selected and divided into normal (CON) and hypertensive (HTN) groups, according to the 2018 Chinese Guidelines for the Management of Hypertension. The oral microbiome composition of saliva samples was determined by 16S rRNA gene sequencing. Results: Although there was no significant difference in α and β diversity between the two groups, systolic and diastolic blood pressure were the most important factors influencing the structure of the oral microbiota. At the phylum level, the relative abundance of the spirochete phylum and the mutualistic bacterial phylum was higher in the HT group than in the CON group (p < 0.05). Diastolic blood pressure was negatively correlated with Streptococcus. Furthermore, we analyzed HTN patients with 120 mmHg<systolic blood pressure<160 mmHg and systolic blood pressure>160 mmHg separately and found that the abundance of Saccharibacteria_(TM7) was significantly increased in the HTN_2 group. Conclusions: Our study identified specific oral microbiota in elderly hypertensive patients, confirming the relationship between oral microbiota and hypertension. This enhances our understanding of the important role of oral microbiota in the pathogenesis of hypertension and accumulates more evidence for microbial involvement in the development of hypertension.
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 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:Animal model implicates microbiota-triggered oral mucosal Th17 cells as drivers of local immunopathology and therapeutic targets in periodontitis.
Project description:Opportunistic oral infections are ultimately presented in a vast majority of HIV-infected patients, often causing debilitating lesions that also contribute to deterioration in nutritional health. Although appreciation for the role that the microbiota is likely to play in the initiation and/or enhancement of oral infections has grown considerably in recent years, little is known about the impact of HIV infection on host-microbe interactions within the oral cavity. In the current study, we characterize modulations in the bacterial composition of the lingual microbiome in patients with treated and untreated HIV infection. Bacterial species profiles were elucidated by microarray assay and compared between untreated HIV infected patients, HIV infected patients receiving antiretroviral therapy, and healthy HIV negative controls. The relationship between clinical parameters (viral burden and CD4+ T cell depletion) and the loss or gain of bacterial species was evaluated in each HIV patient group. Characterization of modulations in the dorsal tongue (lingual) microbiota that are associated with chronic HIV infection.
Project description:Understanding the impact of the microbiota on oral mucosal epithelial barriers, particularly within the gingiva, is essential for elucidating the mechanisms underlying oral health and disease. The gingiva exhibits intricate tissue architecture and undergoes dynamic microenvironmental shifts influenced by various factors. Notably, microbial colonization emerges as an early-life factor that plays a significant role in shaping the functional and immunological maturation of the gingival epithelium. This study utilizes spatial transcriptomic analysis to unveil distinct immunological characteristics between the buccal and palatal regions of the murine gingiva, impacting natural alveolar bone loss. Moreover, the analysis identifies a significant influence of the microbiota on the development and function of the junctional epithelium, which faces the oral microbial plaque, offering new insights into neutrophil recruitment to this strategic location. Additionally, the microbiota is found to impact fundamental functions of the gingival epithelium, including proliferation kinetics and barrier sealing. In conclusion, this study emphasizes the crucial role played by the microbiota in regulating gingival barriers and brings attention to its unique influence on specific epithelial regions within the gingiva.
Project description:Understanding the impact of the microbiota on oral mucosal epithelial barriers, particularly within the gingiva, is essential for elucidating the mechanisms underlying oral health and disease. The gingiva exhibits intricate tissue architecture and undergoes dynamic microenvironmental shifts influenced by various factors. Notably, microbial colonization emerges as an early-life factor that plays a significant role in shaping the functional and immunological maturation of the gingival epithelium. This study utilizes spatial transcriptomic analysis to unveil distinct immunological characteristics between the buccal and palatal regions of the murine gingiva, impacting natural alveolar bone loss. Moreover, the analysis identifies a significant influence of the microbiota on the development and function of the junctional epithelium, which faces the oral microbial plaque, offering new insights into neutrophil recruitment to this strategic location. Additionally, the microbiota is found to impact fundamental functions of the gingival epithelium, including proliferation kinetics and barrier sealing. In conclusion, this study emphasizes the crucial role played by the microbiota in regulating gingival barriers and brings attention to its unique influence on specific epithelial regions within the gingiva.
Project description:Understanding the impact of the microbiota on oral mucosal epithelial barriers, particularly within the gingiva, is essential for elucidating the mechanisms underlying oral health and disease. The gingiva exhibits intricate tissue architecture and undergoes dynamic microenvironmental shifts influenced by various factors. Notably, microbial colonization emerges as an early-life factor that plays a significant role in shaping the functional and immunological maturation of the gingival epithelium. This study utilizes spatial transcriptomic analysis to unveil distinct immunological characteristics between the buccal and palatal regions of the murine gingiva, impacting natural alveolar bone loss. Moreover, the analysis identifies a significant influence of the microbiota on the development and function of the junctional epithelium, which faces the oral microbial plaque, offering new insights into neutrophil recruitment to this strategic location. Additionally, the microbiota is found to impact fundamental functions of the gingival epithelium, including proliferation kinetics and barrier sealing. In conclusion, this study emphasizes the crucial role played by the microbiota in regulating gingival barriers and brings attention to its unique influence on specific epithelial regions within the gingiva.