Dataset Information

Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses.

ABSTRACT: Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the prediabetic state. These data provide scientific community valuable metabolic signatures that become the basis for understanding the impact of periodontitis on a systemic disease and potentially targets for therapeutic intervention.

SUBMITTER: Ilievski V

PROVIDER: S-EPMC4932845 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses.

Ilievski Vladimir V Kinchen Jason M JM Prabhu Ramya R Rim Fadi F Leoni Lara L Unterman Terry G TG Watanabe Keiko K

Journal of oral biology (Northborough, Mass.) 20160423 1

Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, ...[more]

PMID: 27390783

Similar Datasets

Project description:IntroductionThe chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with a wide range of brain-related phenotypes including schizophrenia spectrum disorders (SCZ), autism spectrum disorders (ASD), anxiety disorders and attention deficit disorders (ADHD). The typically deleted region in 22q11.2DS contains multiple genes which haploinsufficiency has the potential of altering the protein and the metabolic profiles.ObjectivesAlteration in metabolic processes and downstream protein pathways during the early brain development may help to explain the increased prevalence of the observed neurodevelopmental phenotypes in 22q11.2DS. However, relatively little is known about the correlation of dysregulated protein/metabolite expression and neurobehavioral impairments in individuals who developed them over time.MethodsIn this study, we performed untargeted metabolic and proteomic analysis in plasma samples derived from 30 subjects including 16 participants with 22q11.2DS and 14 healthy controls (TD) enrolled in a longitudinal study, aiming to identify a metabolic and protein signature informing about the underlying mechanisms involved in disease development and progression. The metabolic and proteomic profiles were also compared between the participants with 22q11.2DS with and without various comorbidities, such as medical involvement, psychiatric conditions, and autism spectrum disorder (ASD) to detect potential changes among multiple specimens, collected overtime, with the aim to understand the basic underlying mechanisms involved in disease development and progression.ResultsWe observed a large number of statistically significant differences in metabolites between the two groups. Among them, the levels of taurine and arachidonic acid were significantly lower in 22q11.2DS compared to the TD group. In addition, we identified 16 proteins that showed significant changes in expression levels (adjusted P < 0.05) in 22q11.2DS as compared to TD, including those involved in 70 pathways such as gene expression, the PI3K-Akt signaling pathway and the complement system. Within participants with 22q11.2DS, no significant changes in those with and without medical or psychiatric conditions were observed.ConclusionTo our knowledge, this is the first report on plasma metabolic and proteomic profiling and on the identification of unique biomarkers in 22q11.2DS. These findings may suggest the potential role of the identified metabolites and proteins as biomarkers for the onset of comorbid conditions in 22q11.2DS. Ultimately, the altered protein pathways in 22q11.2DS may provide insights of the biological mechanisms underlying the neurodevelopmental phenotype and may provide missing molecular outcome measures in future clinical trials to assess early-diagnosis treatment and the efficacy of response to targeted treatment.

Dataset Information

Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses.

Publications

Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets