Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity

Cell Host Microbe. 2017 Jul 12;22(1):120-128.e4. doi: 10.1016/j.chom.2017.06.014.

Abstract

Diabetes is a risk factor for periodontitis, an inflammatory bone disorder and the greatest cause of tooth loss in adults. Diabetes has a significant impact on the gut microbiota; however, studies in the oral cavity have been inconclusive. By 16S rRNA sequencing, we show here that diabetes causes a shift in oral bacterial composition and, by transfer to germ-free mice, that the oral microbiota of diabetic mice is more pathogenic. Furthermore, treatment with IL-17 antibody decreases the pathogenicity of the oral microbiota in diabetic mice; when transferred to recipient germ-free mice, oral microbiota from IL-17-treated donors induced reduced neutrophil recruitment, reduced IL-6 and RANKL, and less bone resorption. Thus, diabetes-enhanced IL-17 alters the oral microbiota and renders it more pathogenic. Our findings provide a mechanistic basis to better understand how diabetes can increase the risk and severity of tooth loss.

Keywords: IL-17; bone loss; diabetes; dysbiosis; microbiota; osteoclast; pathogen; periodontitis.

MeSH terms

  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / etiology
  • Alveolar Bone Loss / microbiology
  • Alveolar Bone Loss / pathology
  • Animals
  • Bacteria / genetics
  • Bacteria / pathogenicity*
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / etiology
  • Bone Resorption / microbiology
  • Colony Count, Microbial
  • DNA, Bacterial
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / immunology*
  • Genes, Bacterial
  • Inflammation
  • Interleukin-17 / immunology*
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / genetics*
  • Mouth / microbiology*
  • Neutrophil Infiltration
  • Osteoclasts
  • Periodontitis / diagnostic imaging
  • Periodontitis / etiology*
  • Periodontitis / microbiology
  • Periodontitis / pathology
  • RANK Ligand / metabolism
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis
  • Tooth Loss / etiology
  • Virulence

Substances

  • DNA, Bacterial
  • Interleukin-17
  • Interleukin-6
  • RANK Ligand
  • RNA, Ribosomal, 16S
  • Tnfsf11 protein, mouse