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:Gut microbiota are known to influence oral drug disposition, yet the specific host pathways they affect remain poorly characterized. This study provides a transcriptome-wide characterization of how physiological gut microbiota regulate the expression of intestinal transporters, phase I and phase II metabolic enzymes, and barrier machinery relevant to oral drug disposition. By identifying microbiota-responsive processes, this work defines the scope of inter-individual variability attributable to gut microbial effects.
Project description:The goal of this study was to understand the link between maternal oral dysbiosis and the gut health of offspring. We demonstrate that maternal oral dysbiosis can have lasting health impacts on offspring. Ligature-induced periodontitis in mothers promotes the expansion of oral pathobionts in the mouth, which are transmitted to the infant gut, rendering offspring more susceptible to enteritis. Notably, although these maternal oral pathobionts are eradicated as the microbiota matures, the imprinted susceptibility to enteritis persists into adulthood.
Project description:Periodontitis is increasingly linked to diverse brain disorders, yet causal mechanisms remain elusive. Here we demonstrate that ligature-induced oral dysbiosis in mice is sufficient to perturb central function. Six weeks of periodontitis produced anxiety-like behavior and motor deficits, accompanied by microglial depletion, reduced neuronal activity and region-selective transcriptional down-regulation in the frontal cortex. Pharmacological microglial ablation phenocopied, and glucocorticoid-receptor blockade rescued, these abnormalities, implicating microglia and activation of the hypothalamic–pituitary–adrenal axis. 16S rRNA gene sequencing revealed significant shifts in oral and gut microbiota that were partially normalized by a broad-spectrum antibiotic cocktail. Antibiotics alone elevated corticosterone but did not affect microglia or behavior, indicating that dysbiosis and glucocorticoids act synergistically on the brain dysfunction. Antibiotic treatment restored microglial density and behaviors in ligature mice, despite plasma corticosterone levels remaining elevated and comparable to those in antibiotic-treated controls. Our findings suggest oral dysbiosis as a tractable driver of neuroimmune dysfunction and redefine periodontitis as a systemic disorder with direct consequences for brain health.
Project description:Periodontitis is increasingly linked to diverse brain disorders, yet causal mechanisms remain elusive. Here we demonstrate that ligature-induced oral dysbiosis in mice is sufficient to perturb central function. Six weeks of periodontitis produced anxiety-like behavior and motor deficits, accompanied by microglial depletion, reduced neuronal activity and region-selective transcriptional down-regulation in the frontal cortex. Pharmacological microglial ablation phenocopied, and glucocorticoid-receptor blockade rescued, these abnormalities, implicating microglia and activation of the hypothalamic–pituitary–adrenal axis. 16S rRNA gene sequencing revealed significant shifts in oral and gut microbiota that were partially normalized by a broad-spectrum antibiotic cocktail. Antibiotics alone elevated corticosterone but did not affect microglia or behavior, indicating that dysbiosis and glucocorticoids act synergistically on the brain dysfunction. Antibiotic treatment restored microglial density and behaviors in ligature mice, despite plasma corticosterone levels remaining elevated and comparable to those in antibiotic-treated controls. Our findings suggest oral dysbiosis as a tractable driver of neuroimmune dysfunction and redefine periodontitis as a systemic disorder with direct consequences for brain health.
Project description:Background: Osteoarthritis (OA) is a globally prevalent degenerative joint disorder that imposes significant socioeconomic burdens. While traditionally viewed as a localized “wear-and-tear” disease, emerging evidence supports a systemic pathogenesis involving the gut-joint axis. The oral-gut-joint pathway remains underexplored in OA pathophysiology. Objective: This study aimed to characterize oral and gut microbiota signatures in knee OA patients and elucidate their functional connections to cartilage degeneration through multiomics integration. Methods: We conducted a cross-sectional observational study involving 25 OA patients and 20 healthy controls. 16S rDNA gene amplicon sequencing region was performed on fecal and oropharyngeal swab samples. Cartilage tissues were subjected to transcriptomic and proteomic analyses. Results: We identified distinct dysbiosis patterns in both the gut and oral microbiomes of OA patients. The α-Diversity of the gut microbiota significantly increased (P < 0.05) with enrichment of Ruminococcaceae and Subdoligranulum. Concurrently, the oral microbiota showed increased α-Diversity and activation of the lipopolysaccharide biosynthesis pathway. We constructed two significant cross-omics correlation modules: one linking gut microbes (Lachnospiraceae and Muribaculaceae) to cartilage inflammatory genes (MAPK11, ITGB3, CD55 and ANGPT2) and extracellular matrix remodelling proteins and another connecting gut microbes (Helicobacter, Pseudomonas, and Phocea) with CXCL14 and GNGT2. Conclusion: Our study revealed the dysbiotic characteristics of the oral-gut microbiome and its complex functional connections with pathological changes in cartilage. These findings offer novel mechanistic insights and potential therapeutic targets for microbiota-based precision interventions in OA.
Project description:Gut microbial profiling of uterine fibroids (UFs) patients comparing control subjects. The gut microbiota was examined by 16S rRNA quantitative arrays and bioinformatics analysis. The goal was to reveal alterations in the gut microbiome of uterine fibroids patients.
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:Those FASTQ are used in a paper where are primarily compared the variations in the oral microbiota composition between HIV patients and healthy controls (HC). In addition, it is performed a longitudinal evaluation of the oral-gut microbiota-immunity axis from HIV-infected patients before starting ART (T0) and after reaching virological suppression (T24 weeks).
Project description:Brain and central nervous system (CNS) tumors are the leading cause of cancer-related deaths in both adults and children, particularly affecting those aged 0–14 years. Efforts to develop targeted therapies have largely been unsuccessful, with limited improvement in survival rates. This underscores the urgent need for more effective treatments. Recent research highlights the importance of the gut microbiota and its collective genomes, known as the microbiome, in maintaining overall health. The microbiome helps prevent infections and regulates immune responses both locally and throughout the body. There is a strong connection between the gastrointestinal (GI) system and the CNS, as the CNS plays a crucial role in controlling the GI tract’s function and balance. The relationship between the gut microbiota and the brain, referred to as the microbiota-gut-brain axis, is a complex interaction that may influence CNS cancer development and treatment outcomes. In this study, researchers examined the gut microbiota composition in a group of pediatric cancer patients, focusing on those with CNS tumors.