title: 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.
authors.affiliation: Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ilievski
authors.affiliation: Metabolon, Inc. Durham, NC, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Kinchen
authors.affiliation: Undergraduate Program, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Ramya
authors.initials: R
authors.lastname: Prabhu
authors.affiliation: Undergraduate Program, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Rim
authors.affiliation: Department of Radiology, University of Chicago, Chicago, IL, USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Leoni
authors.affiliation: Departments of Medicine and Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, and Jesse Brown VA Medical Center, Chicago, IL, USA.
authors.forename: Terry G
authors.initials: TG
authors.lastname: Unterman
authors.affiliation: Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Watanabe
keywords: Experimental periodontitis; Global metabolomic analysis; Prediabetes